Oxazolidinone antibacterial agents having a thiocarbonyl functionality

ABSTRACT

The present invention provides compounds of Formula 1                    
     or pharmaceutical acceptable salts thereof wherein A, G and R, are as defined in the claims which are antibacterial agents.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of co-pending application U.S. Ser No. 09/080,751, filed May 18, 1998, which claims the benefit of provisional application U.S. Ser. No. 60/048,342, filed May 30, 1997, under 35 USC 119(e)(i).

BACKGROUND OF THE INVENTION

The present invention relates to new and useful oxazolidinone compounds and their preparations, and more particularly to oxazolidinone compounds in which the carbonyl functionality of -NH-C(O)-R is converted to a thiocarbonyl functionality, such as a thiourea -NH-C(S)-NH₂, an alkyl thiourea -NH-C(S)-NH-(C₁₋₄ alkyl), thioamide-NH-C(S)-(C₁₋₄ alkyl) or -NH-C(S)-H.

Replacement of the oxygen atom with a sulfur atom has unexpectedly improved the antimicrobial properties of the compounds. The compounds are useful antimicrobial agents, effective against a number of human and veterinary pathogens, including Gram-positive aerobic bacteria such as multiply-resistant staphylococci and streptococci, Gram-negative organisms such as H. influenzae and M. catarrahlis as well as anaerobic organisms such as bacteroides and clostridia species, and acid-fast organisms such as Mycobacterium tuberculosis and Mycobacterium avium. The compounds are particularly useful because they are effective against the latter organisms which are known to be responsible for infection in persons with AIDS.

SUMMARY OF THE INVENTION

In one aspect the subject invention is a compound of the Formula I

or pharmaceutical acceptable salts thereof wherein:

G is

R₁ is

a) H,

b) NH₂,

c) NH-C₁₋₄ alkyl,

d) C₁₋₄ alkyl,

e) -OC₁₋₄ alkyl,

f) -S C₁₋₄ alkyl,

g) C₁₋₄ alkyl substituted with 1-3 F, 1-2 Cl, CN or -COOC₁₋₄ alkyl,

h) C₃₋₆ cycloalkyl,

i) N(C₁₋₄ alkyl)₂ or

j) N(CH₂)₂₋₅;

A is

d) a 5-membered heteroaromatic moiety having one to three atoms selected from the group consisting of S, N, and O, wherein the 5-membered heteroaromatic moiety is bonded via a carbon atom,

wherein the 5-membered heteroaromatic moiety can additionally have a fused-on benzene or naphthyl ring,

wherein the heteroaromatic moiety is optionally substituted with one to three R₄₈,

e) a 6-membered heteroaromatic moiety having at least one nitrogen atom,

wherein the heteroaromatic moiety is bonded via a carbon atom,

wherein the 6-membered heteroaromatic moiety can additionally have a fused-on benzene or naphthyl ring,

wherein the heteroaromatic moiety is optionally substituted with one to three R₅₅,

f) a β-carbolin-3-yl, or indolizinyl bonded via the 6-membered ring, optionally substituted with one to three R₅₅,

wherein R₂ is

a) H,

b) F,

c) Cl,

d) Br,

e) C₁₋₃ alkyl,

f) NO₂, or

g) R₂ and R₃ taken together are -O-(CH₂)_(h)-O-;

R₃ is

a) -S(═O)_(i) R₄,

b) -S(═O)₂-N═S(O)_(j)R₅R₆,

c) -SC(═O)R₇,

d) -C(═O)R₈,

e) -C(═O)R₉,

f) -C(═O)NR₁₀R₁₁,

g) -C(═NR₁₂)R₈,

h) -C(R₈)(R₁₁)-OR₁₃,

i) -C(R₉)(R₁₁)-OR₁₃,

j) -C(R₈)(R₁₁)-OC(═O)R₁₃,

k) -C(R₉)(R₁₁)-OC(═O)R₁₃,

l) -NR₁₀R₁₁,

m) -N(R₁₀)-C(═O)R₇,

n) -N(R₁₀)-S(═O)_(i)R₇,

o) -C(OR₁₄)(OR₁₅)R₈,

p) -C(R₈)(R₁₆)-NR₁₁, or

q) C₁₋₈ alkyl substituted with one or more ═O other than at alpha position, -S(═O)_(i)R₁₇, -NR₁₀R₁₁, C₂₋₅ alkenyl, or C₂₋₅ alkynyl;

R₄ is

a) C₁₋₄ alkyl optionally substituted with one or more halos, OH, CN, NR₁₀R₁₁, or -CO₂R₁₃,

b) C₂₋₄ alkenyl,

c) -NR₁₆R₁₈,

d) -N₃,

e) -NHC(═O)R₇,

f) -NR₂₀C(═O)R₇,

g) -N(R₁₉)₂,

h) -NR₁₆R₁₉, or

i) -NR₁₉R₂₀,

R₅ and R₆ at each occurrence are the same or different and are

a) C₁₋₂ alkyl, or

b) R₅ and R₆ taken together are -(CH₂)_(k)-;

R₇ is C₁₋₄ alkyl optionally substituted with one or more halos;

R₈ is

a) H, or

b) C₁₋₈ alkyl optionally substituted with one or more halos, or C₃₋₈ cycloalkyl;

R₉ is C₁₋₄ alkyl substituted with one or more

a) -S(═O)R₁₇,

b) -OR₁₃,

c) -OC(═O)R₁₃,

d) -NR₁₀R₁₁, or

e) C₁₋₅ alkenyl optionally substituted with CHO;

R₁₀ and R₁₁ at each occurrence are the same or different and are

a) H,

b) C₁₋₄ alkyl, or

c) C₃₋₈ cycloalkyl;

R₁₂ is

a) -NR₁₀R₁₁,

b) -OR₁₀; or

c) -NHC(═O)R₁₀;

R₁₃ is

a) H, or

b) C₁₋₄ alkyl;

R₁₄ and R₁₅ at each occurrence are the same or different and are

a) C₁₋₄ alkyl, or

b) R₁₄ and R₁₅ taken together are -(CH)₁-;

R₁₆ is

a) H,

b) C₁₋₄ alkyl, or

c) C₁₋₄ cycloalkyl;

R₁₇ is

a) C₁₋₄ alkyl, or

b) C₃₋₈ cycloalkyl;

R₁₈ is

a) H)

b) C₁₋₄ alkyl,

c) C₂₋₄ alkenyl,

d) C₃₋₄ cycloalkyl,

e) -OR₁₃ or

f) -NR₂₁R₂₂;

R₁₉ is

a) Cl,

b) Br, or

c) I;

R₂₀ is a physiologically acceptable cation;

R₂₁ and R₂₂ at each occurrence are the same or different and are

a) H,

b) C₁₋₄ alkyl, or

c) -NR₂₁R₂₂ taken together are -(CH₂)_(m)-;

wherein R₂₃ and R₂₄ at each occurrence are the same or different and are

a) H,

b) F,

c) Cl,

d) C₁₋₂ alkyl,

e) CN

f) OH,

g) C₁₂ alkoxy,

h) nitro, or

i) amino;

Q is

m) a diazinyl group optionally substituted with X and Y,

n) a triazinyl group optionally substituted with X and Y,

o) a quinolinyl group optionally substituted with X and Y,

p) a quinoxalinyl group optionally substituted with X and Y.

q) a naphthyridinl group optionally substituted with X and Y,

Q and R₂₄ taken together are

wherein Z¹ is

a) -CH₂-,

b) -CH(R¹⁰⁴)-CH₂-,

c) -C(O)-, or

d) -CH₂CH₂CH₂-;

wherein Z² is

a) -O₂S-,

b) -O-,

c) -N(R¹⁰⁷)-,

d) -OS-, or

e) -S-;

wherein Z³ is

a) -O₂S-,

b) -O-,

c) -OS-, or

d) -S-;

wherein A¹ is

a) H-, or

b) CH₃;

wherein A² is

a) H-,

b) HO-,

c) CH₃-,

d) CH₃O-,

e) R¹⁰²-CH₂-C(O)-NH-

f) R103O-C(O)-NH-,

g) (C₁-C₂)alkyl-O-C(O)-,

h) HO-CH₂-,

i) CH₃O-NH-,

j) (C₁-C₃)alkyl-O₂C-

k) CH₃-C(O)-,

l) CH₃-C(O)-CH₂-,

A¹ and A² taken together are:

wherein R¹⁰² is

a) H-,

b) CH₃-,

c) phenyl-CH₂-, or

d) CH₃C(O)-;

wherein R103 is

a) (C₁-C₃)alkyl-, or

b) phenyl-;

wherein R¹⁰⁴ is

a) H-, or

b) HO-;

wherein R¹⁰⁵ is

a) H-,

b) (C₁-C₃)alkyl-,

c) CH₂═CH-CH₂-, or

d) CH₃-O-(CH₂)₂-;

wherein R¹⁰⁶ is

a) CH₃-C(O)-,

b) H-C(O)-,

c) Cl₂CH-C(O)-,

d) HOCH₂-C(O)-,

e) CH₃SO₂-,

g) F₂CHC(O)-,

i) H₃C-C(O)-O-CH₂-C(O)-,

j) H-C(O)-O-CH₂-C(O)-,

l) HC≡C-CH₂O-CH₂-C(O)-, or

m) phenyl-CH₂-O-CH₂-C(O)-;

wherein R¹⁰⁷ is

a) R¹⁰²O-C(R¹¹⁰)(R¹¹¹)-C(O)-,

b) R103O-C(O)-,

c) R¹⁰⁸-C(O)-,

f) H₃C-C(O)-(CH₂)₂-C(O)-,

g) R¹⁰⁹-SO₂-,

i) HO-CH₂-C(O)-,

j) R¹¹⁶-(CH₂)₂-,

k) R¹¹³-C(O)-O-CH₂-C(O)-,

l) (CH₃)₂N-CH₂-C(O)-NH-,

m) NC-CH₂-,

n) F₂-CH-CH₂-, or

o) R¹⁵⁰R¹⁵¹NSO₂

wherein R¹⁰⁸ is

a) H-,

b) (C₁-C₄)alkyl,

c) aryl -(CH₂)_(p),

d) ClH₂C-,

e) Cl₂HC-,

f) FH₂C-,

g) F₂HC-,

h) (C₃-C₆)cycloalkyl, or

i) CNCH₂-.

wherein R¹⁰⁹ is

a) alkyl C₁-C₄,

b) -CH₂Cl

c) -CH₂CH═CH₂,

d) aryl, or

e) -CH₂CN;

wherein R¹¹⁰ and R¹¹¹ are independently

a) H-,

b) CH₃-; or

wherein R¹¹² is

a) H-,

b) CH₃O-CH₂O-CH₂-, or

c) HOCH₂-;

wherein R¹¹³ is

a) CH₃-,

b) HOCH₂-,

c) (CH₃)₂N-phenyl, or

d) (CH₃)2N-CH₂-;

wherein R¹¹⁴ is

a) HO-,

b) CH₃O-,

c) H₂N-,

d) CH₃O-C(O)-O-,

e) CH₃-C(O)-O-CH₂-C(O)-O-,

f) phenyl-CH₂-O-CH₂-C(O)-O-,

g) HO-(CH₂)₂-O-,

h) CH₃O-CH₂-O-(CH₂)₂-O-, or

i) CH₃O-CH₂-O-;

wherein R¹¹³ is

a) CH₃-,

b) HOCH₂-,

c) (CH₃)₂N-phenyl, or

d) (CH₃)₂N-CH₂-;

wherein R¹¹⁵ is

a) H-, or

b) Cl-;

wherein R¹¹⁵ is

a) HO-

b) CH₃O-, or

c) F;

wherein R¹⁵⁰ and R¹⁵¹ are each H or alkyl C₁-C₄ or R¹⁵⁰ and R¹⁵¹ taken together with the nitrogen atom to which each is attached form a monocyclic heterocyclic ring having from 3 to 6 carbon atoms;

B is an unsaturated 4-atom linker having one nitrogen and three carbons;

M is

a) H,

b) C₁₋₈ alkyl,

c) C₃₋₈ cycloalkyl,

d) -(CH₂)_(m)OR₁₃, or

e) -(CH₂)_(h)-NR₂₁R₂₂;

Z is

a) O,

b) S, or

c) NM;

W is

a) CH,

b) N, or

c) S or O when Z is NM;

Y is

a) H,

b) F,

c) Cl,

d) Br,

e) C₁₋₃ alkyl, or

f) NO₂;

X is

a) H,

b) -CN,

c) OR₂₇,

d) halo,

e) NO₂,

f) tetrazoyl,

g) -SH,

h) -S(═O)_(i)R₄,

i) -S(═O)₂-N═S(O)_(j)R₅R₆,

j) -SC(═O)R₇,

k) -C(═O)R₂₅,

m) -C(═NR₉)R₂₅,

n) -C(R₂₅)(R₂₈)-OR₁₃,

o) -C(R₂₅)(R₂₈)-OC(═O)R₁₃,

p) -C(R₂₅)(OR₁₃)-(CH₂)_(h)-NR₂₇R₂₈,

q) -NR₂₇R₂₈,

r) -N(R₂₇)C(═O)R₇,

s) -N(R₂₇)-S(═O)_(i)R₇,

t) -C(OR₁₄)(OR₁₅)R₁₈,

u) -C(R₂₅)(R₁₆)-NR₂₇R₂₅, or

v) C₁₋₈ alkyl substituted with one or more halos, OH, ═O other than at alpha position, -S(═O)_(i)R₁₇, -NR₂₇R₂₈, C₂₋₅ alkenyl, C₂₋₅ alkynyl, or C₃₋₈ cycloalkyl;

R₄, R₅, R₆, R₇, R₁₄, R₁₅, R₁₆, and R₁₇ are the same as defined above;

R₂₅ is

a) H,

b) C₁₋₈ alkyl optionally substituted with one or more halos, C₃₋₈ cycloalkyl, C₁₋₄alkyl substituted with one or more of -S(═O)_(i)R₁₇, -OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or

c) C₂₋₅ alkenyl optionally substituted with CHO, or CO₂R₁₃;

R₂₆ is

a) R₂₈, or

b) NR₂₇N₂₈;

R₂₇and R₂₈ at each occurrence are the same or different and are

a) H,

b) C₁₋₈ alkyl,

c) C₃₋₈ cycloalkyl,

d) -(CH₂)_(m)OR₁₃,

e) -(CH₂)_(h)-NR₂₁R₂₂, or

f) R₂₇ and R₂₈ taken together are -(CH₂)₂O(CH₂)₂-, -(CH₂)_(h)CH(COR₇)-, or -(CH₂)₂N(CH₂)₂(R₇);

R₂₉ is

a) -NR₂₈,

b) -OR, or

c) -NHC(═O)R₂₈;

wherein R₃₀ is

a) H,

b) C₁₋₈ alkyl optionally substituted with one or more halos, or

c) C₁₋₈ alkyl optionally substituted with one or more OH, or C₁₋₆alkoxy;

wherein E is

a) NR₃₉,

b) -S(═O)_(i), or

c) O;

R₃₈ is

a) H,

b) C₁₋₆ alkyl,

c) -(CH₂)_(q)-aryl, or

d) halo;

R₃₉ is

a) H,

b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or -CN,

c) -(CH₂)_(q)-aryl,

d) -CO₂R₄₀,

e) -COR₄₁,

f) -C(═O)-(CH₂)_(q),C(═O)R₄₀,

g) -S(═O)₂-C₁₋₆ alkyl,

h) -S(═O)₂-(CH₂)_(q)-aryl, or

i) -(C═O)_(j)-Het;

R₄₀ is

a) H,

b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or -CN,

c) -(CH₂)_(q)-aryl, or

d) -(CH₂)_(q)-OR₄₂;

R₄₁ is

a) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or -CN,

b) -(CH₂)_(q)-aryl, or

c) (CH₂)_(q)-OR₄₂;

R₄₂ is

a) H,

b) C₁₋₆ alkyl,

c) -(CH₂)_(q)-aryl, or

d) -C(═O)-C₁₋₆ alkyl;

aryl is

a) phenyl,

b) pyridyl, or

c) napthyl; a to c optionally substituted with one or more halo, -CN, OH, SH, C₁₋₆alkyl, C₁₋₆ alkoxy, or C₁₋₆alkylthio;

wherein R₄₃ is

a) H,

b) C₁₋₂ alkyl,

c) F, or

d) OH;

R₄₄ is

a) H,

b) CF₃,

c) C₁₋₃ alkyl optionally substituted with one or more halo,

d) phenyl optionally substituted with one or more halo,

e) R₄₄ and R₄₅ taken together are a 5-, 6-, or 7-membered ring of the formula,

or

f) R₄₄ and R₄₅ taken together are -(CH₂)_(k)-, when R₄₆ is an electron-withdrawing group;

R₄₅ and R₄₆ at each occurrence are the same or different and are

a) an electron-withdrawing group,

b) H,

c) CF₃,

d) C₁₋₃ alkyl optionally substituted with one halo,

e) phenyl, provided at least one of R₄₅ or R₄₆ is an electron-withdrawing group, or

f) R₄₅ and R₄₆ taken together are a 5-, 6-, 7-membered ring of the formula

U is

a) CH₂,

b) O,

c) S, or

d) NR₄₇;

R₄₇ is

a) H, or

b) C₁₋₅ alkyl;

wherein R₄₈ is

a) carboxyl,

b) halo,

c) -CN,

d) mercapto,

e) formyl,

f) CF₃,

g) -NO₂,

h) C₁₋₆ alkoxy,

i) C₁₋₆ alkoxycarbonyl,

j) C₁₋₆ alkythio,

k) C₁₋₆ acyl,

l) -NR₄₉ R₅₀,

m) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅ acyl, or -NR₄₉R₅₀,

n) C₂₋₈ alkenylphenyl optionally substituted with one or two R₅₁,

o) phenyl optionally substituted with one or two R₅₁,

p) a 5-, or 6-membered (un)saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with one or two R₅₁, or

q)

R₄₉ and R₅₀ at each occurrence are the same or different and are

a) H,

b) C₁₋₄ alkyl,

c) C₅₋₆ cycloalkyl, or

d) R₄₉ and R₅₀ taken together with the nitrogen atom is a 5-, 6-membered saturated heterocyclic moiety which optionally has a further hetero atom selected from the group consisting of S, N, and O, and can in turn be optionally substituted with, including on the further nitrogen atom, C₁₋₃ alkyl, or C₁₋₃ acyl;

R₅₁ is

a) carboxyl,

b) halo,

c) -CN,

d) mercapto,

e) formyl,

f) CF₃,

g) -NO₂,

h) C₁₋₆ alkoxy,

i) C₁₋₆ alkoxycarbonyl,

j) C₁₋₆ alkythio,

k) C₁₋₆ acyl,

l) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅ acyl, or -NR₄₉R₅₀,

m) phenyl,

n) -C(═O)NR₅₂R₅₃

o) -NR₄₉R₅₀,

p) -N(R₅₂)(-SO₂R₅₄),

q) -SO₂-NR₅₂R₅₃, or

r) -S(═O)_(j)R₅₄;

R₅₂ and R₅₃ at each occurrence are the same or different and are

a) H,

b) C₁₋₆ alkyl, or

c) phenyl;

R₅₄ is

a) C₁₋₄ alkyl, or

b) phenyl optionally substituted with C₁₋₄ alkyl;

wherein R₅₅ is

a) carboxyl,

b) halo,

c) -CN,

d) mercapto,

e) formyl,

f) CF₃,

g) -NO₂,

h) C₁₋₆ alkoxy,

i) C₁₋₆ alkoxycarbonyl,

j) C₁₋₆ alkythio

k) C₁₋₆ acyl,

l) -NR₅₆ R₅₇,

m) C₁₋₆ alkyl optionally substituted with OH, Cl alkoxy, C₁₋₅ acyl, or -NR₅₆R₅₇,

n) C₂₋₈ alkenylphenyl optionally substituted with one or two R₅₈,

o) phenyl optionally substituted with one or two R₅₈,

p) a 5- or 6-membered (un)saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with one or two R₅₈, or

q)

R₅₆ and R₅₇ at each occurrence are the same or different and are

a) H,

b) formyl,

c) C₁₋₄ alkyl,

d) C₁₋₄ acyl,

e) phenyl,

f) C₃₋₆ cycloalkyl, or

g) R₁₆ and R₁₇ taken together with the nitrogen atom is a 5-, 6-membered saturated heterocyclic moiety which optionally has a further hetero atom selected from the group consisting of S, N, and O, and can in turn be optionally substituted with, including on the further nitrogen atom, phenyl, pyrimidyl, C₁₋₃ alkyl, or C₁₋₃ acyl;

R₅₈is

a) carboxyl,

b) halo,

c) -CN,

d) mercapto,

e) formyl,

f) CF₃,

g) -NO₂,

h) C₁₋₆ alkoxy,

i) C₁₋₆ alkoxycarbonyl,

j) C₁₋₆ alkythio,

k) C₁₋₆ acyl,

l) phenyl,

m) C₁₋₆ alkyl optionally substituted with OH, azido, C₁₋₅ alkoxy, C₁₋₅ acyl, -NR₆₅R₆₆, -SR₆₇, -O-SO₂R₆₈, or

n) -C(═O)NR₅₉ R₆₀,

o) -NR₅₆R₅₇,

p) -N(R₅₉)(-SO₂R₅₄),

r) -S(═O)_(i)R₅₄,

s) -CH═N-R₆₁, or

t) -CH(OH)-SO₃R₆₄;

R₅₄ is the same as defined above;

R₅₉ and R₆₀ at each occurrence are the same or different and are

a) H,

b) C₁₋₆ alkyl,

c) phenyl, or

d) tolyl;

R₆₁ is

a) OH,

b) benzyloxy,

c) -NH-C(═O)-NH₂,

d) -NH-C(═S)-NH₂, or

e) -NH-C(═NH)-NR₂R₆₃;

R₆₂ and R₆₃ at each occurrence are the same or different and are

a) H, or

b) C₁₋₄ alkyl optionally substituted with phenyl or pyridyl;

R₆₄ is

a) H, or

b) a sodium ion;

R₆₅ and R₆₆ at each occurrence are the same or different and are

a) H,

b) formyl,

c) C₁₋₄ alkyl,

d) C₁₋₄ acyl,

e) phenyl,

f) C₃₋₆ cycloalkyl,

g) R₆₅ and R66 taken together are a 5-, 6-membered saturated heterocyclic moiety having one to three atoms selected from the group consisting, of S, N, and O, optionally substituted with, including on the nitrogen atom, phenyl, pyrimidyl, C₁₋₃ alkyl, or C₁₋₃ acyl,

h) -P(O)(OR₇₀)(OR₇₁), or

i) -SO₂-R₇₂;

R₆₇ is

R₆₉ is

a) C₁₋₆alkoxycarbonyl, or

b) carboxyl;

R₇₀ and R₇₁ at each occurrence are the same or different and are

a) H, or

b) C₁₋₃ alkyl;

R₇₂ is

a) methyl,

b) phenyl, or

c) tolyl;

wherein K is

a) O, or

b) S;

R₇₃, R₇₄, R₇₅, R₇₆, and R₇₇ at each occurrence are the same or different and are

a) H,

b) carboxyl,

c) halo,

d) -CN,

e) mercapto,

f) formyl,

g) CF₃,

h) -NO₂,

i) C₁₋₆ alkoxy,

j) C₁₋₆ alkoxycarbonyl,

k) C₁₋₆ alkythio,

l) C₁₋₆ acyl,

m) -NR₇₈R₇₉,

n) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅ acyl, -NR₇₈R₇₉, -N(phenyl)(CH₂-CH₂-OH), -O-CH(CH₃)(OCH₂CH₃), or -O-phenyl-[para-NHC(═O)CH₃],

o) C₂₋₈ alkenylphenyl optionally substituted with R₅₁,

p) phenyl optionally substituted with R₅₁, or

q) a 5-, or 6-membered (un)saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, optionally substituted with R₅₁;

R₅₁ is the same as defined above;

R₇₈ and R₇₉ at each occurrence are the same or different and are

a) H,

b) C₁₋₄ alkyl,

c) phenyl, or

d) R₇₈ and R₇₉ taken together with the nitrogen atom is a 5-, 6-membered saturated heterocyclic moiety which optionally has a further hetero atom selected from the group consisting of S, N, and O, and can in turn be optionally substituted with, including on the further nitrogen atom, C₁₋₃ alkyl, or C₁₋₃ acyl;

wherein T is

a) O,

b) S, or

c) SO₂;

R₇₅, R₇₆, and R₇₇ are the same as defined above;

R₈₀ is

a) H,

b) formyl,

c) carboxyl,

d) C₁₋₆ alkoxycarbonyl,

e) C₁₋₈ alkyl,

f) C₂₋₈ alkenyl,

wherein the substituents (e) and (f) can be optionally substituted with OH, halo, C₁₋₆ alkoxy, C₁₋₆acyl, C₁₋₆ alkylthio or C₁₋₆ alkoxycarbonyl, or phenyl optionally substituted with halo,

g) an aromatic moiety having 6 to 10 carbon atoms optionally substituted with carboxyl, halo, -CN, formyl, CF₃, -NO₂, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ acyl, C₁₋₆ alkylthio, or C₁₋₆alkoxycarbonyl;

h) -NR₈₁R₈₂,

i) -OR₉₀,

j) -S(═O)_(i)-R₉₁,

k) -SO₂-N(₂)(R₉₃), or

l) a radical of the following formulas:

R₈₁ and R₈₂ at each occurrence are the same or different and are

a) H,

b) C₃₋₆ cycloalkyl,

c) phenyl,

d) C₁₋₆ acyl,

e) C₁₋₈ alkyl optionally substituted with OH, C₁₋₆ alkoxy which can be substituted with OH, a 5-, or 6-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, phenyl optionally substituted with OH, CF₃, halo, -NO₂, C₁₋₄ alkoxy, -NR₈₃R₈₄, or

V is

a) O,

b) CH₂, or

c) NR₈₇;

R₈₃ and R₈₄ at each occurrence are the same or different and are

a) H, or

b) C₁₋₄ alkyl;

R₈₅ is

a) OH,

b) C₁₋₄ alkoxy, or

c) -NR₈₈R₈₉;

R₈₆ is

a) H, or

b) C₁₋₇ alkyl optionally substituted with indolyl, OH, mercaptyl, imidazoly, methylthio, amino, phenyl optionally substituted with OH, -C(═O)-NH₂, -CO₂H, or -C(═NH)-NH₂;

R₈₇ is

a) H,

b) phenyl, or

c) C₁₋₆ alkyl optionally substituted by OH;

R₈₈ and R₈₉ at each occurrence are the same or different and are

a) H,

b) C₁₋₅ alkyl

c) C₃₋₆ cycloalky, or

d) phenyl;

R₉₀ is

a) C₁₋₈ alkyl optionally substituted with C₁₋₆ alkoxy or C₁₋₆ hydroxy, C₃₋₆ cycloalkyl, a 6-membered aromatic optionally benzo-fused heterocyclic moiety having one to three nitrogen atoms, which can in turn be substituted with one or two -NO₂, CF₃, halo, -CN, OH, C₁₋₅ alkyl, C₁₋₅ alkoxy, or C₁₋₅ acyl;

b)

c) phenyl, or

d) pyridyl;

R₉₁ is

a) C₁₋₆ alkyl,

b) C₂₋₁₆ alkenyl,

wherein the substituents (a) and (b) can be optionally substituted with C₁₋₆ alkoxycarbonyl, or a 5-, 6-, 7-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O,

c) an aromatic moiety having 6 to 10 carbon atoms, or

d) a 5-, 6-, 7-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O,

wherein the substituents (c) and (d) can be optionally substituted with carboxyl, halo, -CN, formyl, CF₃, -NO₂, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ acyl, C₁₋₆ alkylthio, or C₁₋₆ alkoxycarbonyl;

R₉₂ and R₉₃ at each occurrence are the same or different and are

a) H,

b) phenyl,

c) C₁₋₆ alkyl, or

d) benzyl;

R₉₄ and R₉₅ at each occurrence are the same or different and are

a) H,

b) OH,

c) C₁₄ alkyl optionally substituted with -NR₈₃R₈₄, or

d) R₉₄ and R₉₅ taken together are ═O;

R₉₆ is

a) an aromatic moiety having 6 to 10 carbon atoms,

b) a 5-, or 6-membered aromatic optionally benzo-fused heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O,

wherein the substituents (a) and (b) which can in turn be substituted with one or three -NO₂, CF₃, halo, -CN, OH, phenyl, C₁₋₅ alkyl, C₁₋₅ alkoxy, or C₁₋₅ acyl,

c) morpholinyl,

d) OH,

e) C₁₋₆ alkoxy,

f) -NR₈₃R₈₄,

g) -C(═O)-R₉₇, or

h)

R₉₇ is

a) morpholinyl,

b) OH, or

c) C₁₋₆ alkoxy;

h is 1, 2,or 3;

i is 0, 1, or 2;

j is 0 or 1;

k is 3, 4, or 5;

l is 2 or 3;

m is 4 or 5;

n is 0, 1, 2, 3, 4, or 5;

p is 0, 1, 2, 3, 4, or 5; with the proviso that n and p together are 1, 2, 3, 4, or 5;

q is 1, 2, 3, or 4;

r is 2, 3, or 4;

t is 0, 1, 2, 3, 4, 5, or 6;

u is 1 or 2;

w is 0, 1, 2, or 3.

DETAILED DESCRIPTION OF THE INVENTION

The new compounds of the invention can be prepared using known compounds and intermediates of oxazolidinones, isoxazolines and butyolactones as intermediates and synthetic methods known in the art. Thioamides of the invention can typically be prepared by the reaction of the corresponding amide with Lawesson's reagent.

Compounds disclosed in the following publications are suitable intermediates for preparation of the compounds of this invention and are hereby incorporated by reference for their disclosure of suitable compounds that can be converted to the subject thiocarbonyl derivatives.

U.S. Pat. Nos. 5,225,565; 5,182,403; 5,164,510; 5,247,090; 5,231,188; 5,565,571; 5,547,950; and 5,523,403.

PCT Application and publications PCT/US93/04850, WO94/01110; PCT/US94/08904, WO95/07271; PCT/US95/02972, WO95/25106; PCT/US95/10992, WO96/13502; PCT/US96/05202, WO96/35691; PCT/US96/12766; PCT/US96/13726; PCT/US96/14135; PCT/US96/17120; PCT/US96/19149; PCT/US97/01970; PCT/US95/12751, WO96/15130; and PCT/US96/00718, WO96/23788.

Chemical conversion techniques for converting various intermediates having a CH₂NH₂ on the oxazolidinone ring to CH2NH-C(S)-CH₃ is disclosed by Hartke, K., Barrmeyer, S., J. prakt. Chem. 1996, 338, 251-6. Similarly, conversion of CH₂NHC(═O)CH₃ to CH₂NHC(S)NHCH₃ is reported by Cava, M. P.; Levinson, M. I., Thionation Reactions of Lawesson's Reagents, Tetrahedron 1985, 41, 5061-87.

For the purpose of the present invention, the carbon content of various hydrocarbon containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety, i.e., the prefix C_(i-j) defines the number of carbon atoms present from the integer “i” to the integer “j”, inclusive. Thus, C₁₋₄ alkyl refers to alkyl of 1-4 carbon atoms, inclusive, or methyl, ethyl, propyl, butyl and isomeric forms thereof.

The terms “C₁₋₂ alkyl”, “C₁₋₃ alkyl, C₁₋₄ alkyl”, “C₁₋₅ alkyl”, “C₁₋₅ alkyl”, “C₁₋₈ alkyl”, and “C₁₋₆ alkyl” refer to an alkyl group having one to two, one to three, one to four, one to five, one to six, one to eight, or one to sixteen carbon atoms respectively such as, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl and their isomeric forms thereof.

The terms “C₂₋₄ alkenyl”, “C₂₋₅ alkenyl”, “C₂₋₈ alkenyl”, “C₂₋₁₄ alkenyl” and “C₂₋₁₆ alkenyl” refer to at least one double bond alkenyl group having two to four, two to five, two to eight, two to fourteen, or two to sixteen carbon atoms, respectively such as, for example, ethenyl, propenyl, butenyl, pentenyl, pentdienyl, hexenyl, hexdienyl, heptenyl, heptdienyl, octenyl, octdienyl, octatrienyl, nonenyl, nonedienyl, nonatrienyl, undecenyl, undecdienyl, dodecenyl, tridecenyl, tetradecenyl and their isomeric forms thereof.

The terms “C₂₋₅ alkynyl”, “C₂₋₈ alkynyl”, and “C₂₋₁₀ alkynyl” refer to at least one triple bond alkynyl group having two to five, two to eight, or two to ten carbon atoms respectively such as, for example, ethynyl, propynyl, butynyl, pentynyl, pentdiynyl, hexynyl, hexdiynyl, heptynyl, heptdiynyl, octynyl, octdiynyl, octatriynyl, nonynyl, nonediynyl, nonatriynyl and their isomeric forms thereof.

The terms “C₃₋₄ cycloalkyl”, “C₃₋₆ cycloalkyl”, “C₅₋₆ cycloalkyl”, and “C₃₋₈ cycloalkyl” refer to a cycloalkyl having three to four, three to six, five to six, or three to eight carbon atoms respectively such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and their isomeric forms thereof.

The terms “C₁₋₄ alkoxy”, “C₁₋₆ alkoxy”, and “C₁₋₈ alkoxy” refer to an alkyl group having one to four, one to six, or one to eight carbon atoms respectively attached to an oxygen atom such as, for example, methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, heptyloxy, or octyloxy and their isomeric forms thereof.

The terms “C₁₋₆ alkylamino”, and “C₁₋₈ alkylamino” refer to an alkyl group having one to six, or one to eight carbon atoms respectively attached to an amino moiety such as, for example, methylamino, ethylamino, propylamino, butylamino, pentylamino, hexylamino, heptylamino, or octoylamino and their isomeric forms thereof.

The terms “C₁₋₆ dialkylamino”, and “C₁₋₈ dialkylamino” refer to two alkyl groups having one to six, or one to eight carbon atoms respectively attached to an amino moiety such as, for example, dimethylamino, methylethylamino, diethylamino, dipropylamino, methypropylamino, ethylpropylamino, dibutylamino, dipentylamino, dihexylamino, methylhecylamino, diheptylamino, or dioctoylamino and their isomeric forms thereof.

The terms “C₁₋₃ acyl”, “C₁₋₄ acyl”, “C₁₋₅ acyl”, “C₁₋₆ acyl”, “C₁₋₈ acyl”, and “C₂₋₈ acyl” refer to a carbonyl group having an alkyl group of one to three, one to four, one to five, one to six, one to eight, or two to eight carbon atoms.

The terms “C₁₋₄ alkoxycarbonyl”, “C₁₋₆ alkoxycarbonyl”, and “C₁₋₈ alkoxycarbonyl” refer to an ester group having an alkyl group of one to four, one to six, or one to eight carbon atoms.

The term “C₁₋₈ alkyl phenyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof which is substituted with at least one phenyl radical.

The term “C₂₋₈ alkenyl phenyl” refers to a at least one double bond alkenyl group having one to eight carbon atoms and isomeric forms thereof which is substituted with at least one phenyl radical.

The term “C₁₋₈ alkyl pyridyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof which is substituted with at least one pyridyl radical.

The term “C₁₋₈ hydroxyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof attached to a hydroxy group.

The term “C₁₋₈ alkylsulfonyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof attached to a SO₂ moiety.

The term “C₁₋₆ alkylthio” refers to an alkyl group having one to six carbon atoms and isomeric forms thereof attached to a sulfur atom.

The term “Het” refers to 5 to 10 membered saturated, unsaturated or aromatic heterocyclic rings containing one or more oxygen, nitrogen, and sulfur forming such groups as, for example, pyridine, thiophene, furan, pyrazoline, pyrimidine, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 3-pyrazinyl, 2-quinolyl, 3-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 2-quinazolinyl, 4-quinazolinyl, 2-quinoxalinyl, 1-phthalazinyl, 4-oxo-2-imidazolyl, 2-imidazolyl, 4-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 4-oxo-2-oxazolyl, 5-oxazolyl, 4,5,-dihydrooxazole, 1,2,3-oxathiole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazole, 4-isothiazole, 5-isothiazole, 2-indolyl, 3-indolyl, 3-indazolyl, 2-benzoxazolyl, 2-benzothiazolyl, 2-benzimidazolyl, 2-benzofuranyl, 3-benzofuranyl, benzoisothiazole, benzisoxazole, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-isopyrrolyl, 4-isopyrrolyl, 5-isopyrrolyl, 1,2,3,-oxathiazole-1-oxide, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 5-oxo-1,2,4-oxadiazol-3-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 3-oxo-1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazol-5-yl, 2-oxo-1,3,4thiadiazol-5-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,3,4-tetrazol-5-yl, 5-oxazolyl, 1- pyrrolyl, 1-pyrazolyl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, 1-tetrazolyl, 1-indolyl, 1-indazolyl, 2-isoindolyl, 7-oxo-2-isoindolyl,1-purinyl, 3-isothiazolyl, 4-isothiazolyl and 5-isothiazolyl, 1,3,4,-oxadiazole, 4-oxo-2-thiazolinyl, or 5-methyl-1,3,4-thiadiazol-2-yl, thiazoledione, 1,2,3,4-thiatriazole, 1,2,4-dithiazolone. Each of these moieties may be substituted as appropriate.

The term halo refers to fluoro, chloro, bromo, or iodo.

The compounds of the present invention can be converted to their salts, where appropriate, according to conventional methods.

The term “pharmaceutically acceptable salts” refers to acid addition salts useful for administering the compounds of this invention and include hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, acetate, propionate, lactate, mesylate, maleate, malate, succinate, tartrate, citric acid, 2-hydroxyethyl sulfonate, fumarate and the like. These salts may be in hydrated form.

When Q is the structure of

the dotted line in the heterocyclic ring means that this bond can be either single or double. In the case where the dotted line is a double bond, the R₃₉ group will not be present.

The compounds of Formula I of this invention contain a chiral center at C5 of the isoxazoline ring, and as such there exist two enantiomers or a racemic mixture of both. This invention relates to both the enantiomers, as well as mixtures containing both the isomers. In addition, depending on substituents, additional chiral centers and other isomeric forms may be present in any of A or R₁ group, and this invention embraces all possible stereoisomers and geometric forms in these groups.

The compounds of this invention are useful for treatment of microbial infections in humans and other warm blooded animals, under both parenteral and oral administration.

The pharmaceutical compositions of this invention may be prepared by combining the compounds of this invention with a solid or liquid pharmaceutically acceptable carrier and, optionally, with pharmaceutically acceptable adjuvants and excipients employing standard and conventional techniques. Solid form compositions include powders, tablets, dispersible granules, capsules, cachets and suppositories. A solid carrier can be at least one substance which may also function as a diluent, flavoring agent, solubilizer, lubricant, suspending agent, binder, tablet disintegrating agent, and encapsulating agent. Inert solid carriers include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, cellulosic materials, low melting wax, cocoa butter, and the like. Liquid form compositions include solutions, suspensions and emulsions. For example, there may be provided solutions of the compounds of this invention dissolved in water and water-propylene glycol and water-polyethylene glycol systems, optionally containing suitable conventional coloring agents, flavoring agents, stabilizers and thickening agents.

Preferably, the pharmaceutical composition is provided employing conventional techniques in unit dosage form containing effective or appropriate amounts of the active component, that is, the compound according to this invention.

The quantity of active component, that is the compound according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular application, the potency of the particular compound, the desired concentration. Generally, the quantity of active component will range between 0.5% to 90% by weight of the composition

In therapeutic use for treating, or combatting, bacterial infections in warm-blooded animals, the compounds or pharmaceutical compositions thereof will be administered orally, parenterally and/or topically at a dosage to obtain and maintain a concentration, that is, an amount, or blood-level of active component in the animal undergoing treatment which will be antibacterially effective. Generally, such antibacterially effective amount of dosage of active component will be in the range of about 0.1 to about 100, more preferably about 3.0 to about 50 mg/kg of body weight/day. It is to be understood that the dosages may vary depending upon the requirements of the patient, the severity of the bacterial infection being treated, and the particular compound being used. Also, it is to be understood that the initial dosage administered may be increased beyond the above upper level in order to rapidly achieve the desired blood-level or the initial dosage may be smaller than the optimum and the daily dosage may be progressively increased during the course of treatment depending on the particular situation. If desired, the daily dose may also be divided into multiple doses for administration, e.g., 2-4 four times per day.

When the compounds according to this invention are administered parenterally, i.e., by injection, for example, by intravenous injection or by other parenteral routes of administration. Pharmaceutical compositions for parenteral administration will generally contain a pharmaceutically acceptable amount of the compound or a soluble salt (acid addition salt or base salt) dissolved in a pharmaceutically acceptable liquid carrier such as, for example, water-for-injection and a buffer to provide a suitably buffered isotonic solution, for example, having a pH of about 3.5-6. Suitable buffering agents include, for example, trisodium orthophosphate, sodium bicarbonate, sodium citrate, N-methylglucamine, L(+)-lysine and L(+)-arginine to name but a few representative buffering agents. The compound of this invention generally will be dissolved in the carrier in an amount sufficient to provide a pharmaceutically acceptable injectable concentration in the range of about 1 mg/mL to about 400 mg/mL of solution. The resulting liquid pharmaceutical composition will be administered so as to obtain the above-mentioned antibacterially effective amount of dosage. The compounds according to this invention are advantageously administered orally in solid and liquid dosage forms.

As a topical treatment an effective amount of Formula I is admixed in a pharmaceutically acceptable gel or cream vehicle that can be applied to the patient's skin at the area of treatment. Preparation of such creams and gels is well known in the art and can include penetration enhancers.

MIC Test Method

The in vitro MICs of test compounds were determined by a standard agar dilution method. A stock drug solution of each analog is prepared in the preferred solvent, usually DMSO:H₂O (1:3). Serial 2-fold dilutions of each sample are made using 1.0 ml aliquots of sterile distilled water. To each 1.0 ml aliquot of drug is added 9 ml of molten Mueller Hinton agar medium. The drug-supplemented agar is mixed, poured into 15×100 mm petri dishes, and allowed to solidify and dry prior to inoculation.

Vials of each of the test organisms are maintained frozen in the vapor phase of a liquid nitrogen freezer. Test cultures are grown overnight at 35° C on the medium appropriate for the organism. Colonies are harvested with a sterile swab, and cell suspensions are prepared in Trypticase Soy broth (TSB) to equal the turbidity of a 0.5 McFarland standard. A 1:20 dilution of each suspension is made in TSB. The plates containing the drug supplemented agar are inoculated with a 0.001 ml drop of the cell suspension using a Steers replicator, yielding approximately 10⁴ to 10⁵ cells per spot. The plates are incubated overnight at 35° C.

Following incubation the Minimum Inhibitory Concentration (MIC μg/ml), the lowest concentration of drug that inhibits visible growth of the organism, is read and recorded. The data is shown in Tables I and II.

TABLE 1 Oxazolidinone MIC Values (Gram+) SAUR SEPI EFAE SPNE SPYO Structure 9213 12084 9217 9912 152 Comparison* 16 4 8 .5 1

Example 3 4 1 2 .25 .5

Comparison* 2 1 2 .5 1

Example 1 1 .25 .5 .13 .13

Example 5 1 .25 .5 <.125 .25

Example 6 2 1 2 .5 1

Comparison* .5 .25 1 .13 .25

Example 2 8 2 4 2 4

*not a compound of the subject invention SAUR: S. aureus SEPI: S. epidermidis EFAE: E. faecalis SPNE: S. pneumoniae SPYO: S. pyogenes

TABLE II SAUR SEPI EFAE SPNE SPYO HINF MCAT EFAE Example No. 9213 MIC 30593 MIC 12712 MIC 9912 MIC 152 MIC 30063 MIC 30610 MIC 9217 MIC  1 1 0.25 0.5 <0.125 <0.125 8 1 0.5  2 8 4 8 2 4 >16 >16 4  3 4 1 1 0.25 0.5 16 4 2  5 1 0.5 0.5 <0.125 0.25 4 2 0.5  6 2 2 2 0.5 1 16 8 2  7 0.5 0.25 0.5 <0.125 0.25 4 1 0.5  8 2 1 0.5 <0.125 0.25 4 2 1  9 0.5 0.25 0.25 <0.125 <0.125 2 0.5 0.25 10 2 1 0.5 <0.125 0.25 2 1 1 11 0.25 0.25 0.25 <0.125 0.25 2 1 0.25 12 1 0.5 0.25 <0.125 <0.125 1 0.5 0.5 13 1 1 2 0.5 1 >16 8 2 14 1 0.5 1 0.25 0.5 8 1 1 15 32 16 32 4 8 >64 64 32 16 8 8 16 2 8 >64 32 16 17 2 2 4 1 2 64 16 4 18 2 1 2 <0.5 1 32 4 2 19 32 16 32 16 16 64 32 32 21 4 4 8 2 4 64 16 8 22, 23 0.5 0.5 1 <0.125 0.25 4 2 1 24 1 0.25 0.5 <0.125 0.25 4 2 0.5 25 0.5 0.25 0.5 <0.125 <0.125 2 2 0.5 26 1 0.5 1 0.25 0.5 16 2 1 27 0.5 0.5 0.5 <0.125 0.25 4 2 1 28 0.5 0.25 0.5 0.25 0.25 2 1 0.5 29 0.25 0.25 0.25 <0.125 <0.125 2 0.5 0.25 30 4 1 0.5 <0.125 0.25 8 2 1 31 2 1 1 <0.125 0.25 4 1 1 32 16 2 2 0.25 0.25 8 2 4 33 4 2 1 0.25 0.25 4 2 4 34 2 1 2 0.5 1 >16 4 2 35 1 0.5 1 0.25 0.5 16 2 1 Key: SAUR 9213: S. aureus SEPI 30593: S. epidermidis EFAE 12712: E. Faecium SPNE 9912: S. pneumoniae SPYO 152: S. pyogenes HINF 30063: Haemophilus influenzae MCAT 30610: Moraxella catarrhalis EFAE 9217: Enterococcus faecalis

As shown in Scheme 1, the intermediates II for the compounds of this invention are also intermediates disclosed in the oxazolidinone patents and published applications hereinabove incorporated by reference. The intermediates IV for this invention are final products (Examples) from the oxazolidinone patents and published applications hereinabove incorporated by reference.

As shown in Scheme 1, Step 1, and illustrated in Example 5, the isothiocyanates MI can be conveniently prepared by allowing the amine intermediates (H) to react with 1,1′-thiocarbonyldi-2(1H)-pyridone in solvents such as methylene chloride at 0 to 25° C. The thioureas (Ia, R′=H, alkyl₁₋₄) can then be prepared as shown in Step 2 by the reaction of m with ammonia or the appropriate primary amines in solvents such as 1,4-dioxane or tetrahydrofuran at 0-50° C.

Alternatively, as illustrated in Example 6 and shown in Step 3, the thioureas can be prepared by allowing H to react with an appropriate isothiocyanate (R′″N=C=S) in solvents such as tetrahydrofuran at 0-50° C. Thioamides (Ib, R″=H, alkyl₁₋₄) are prepared by allowing H to react with an appropriate dithioester (R′″S-C(═S)-R″, Step 4 as illustrated in Example 4. This reaction is carried out in aqueous-alcoholic solvents at 0-50° C. in the presence of an equivalent of an alkali metal hydroxide.

This reaction, especially when R′″ is methyl or ethyl, can be catalyzed by an alkali metal fluoride.

The reaction of II with R′″-S-C(S)-R′″(R′″=CH₃, C₂H₅) to give Ib (Step 4) can also be carried out in the presence of a tertiary amine base such as triethylaniline in solvents such as THF, dioxane or methylene chloride at 10-50° C. for 3-48 hr.

When the reaction conditions are tolerated by the substituents on R (see, for example, Examples 1-3) the thioamides (Ib, R′- H, alkyl₁₋₄) can also be conveniently prepared (Step 5) by allowing the appropriate amide intermediates (I) to react with reagents such as 2,4-bis(methoxyphenyl)-1,3-dithiadiphosphetane-2,4-disulfide (Lawesson's Reagent) in 1,4-dioxane, benzene, toluene or tetrahydrofuran at 60-110° C.; phosphorus decasulfide and sodium carbonate in tetrahydrofuran at 20-50° C. [Brillon, D., Synthetic Communications, 20, 3085 (1990)] or phosphorus decasulfide and sodium fluoride in 1,2-dimethoxyethane at 20-50° C. [Hartke, K., Gerber, H.-D., J. Prakt. Chem., 338, 763 (1996)].

Compounds Ic are prepared (Step 6) by allowing II to react first with carbon disulfide and a tertiary amine base such as triethylamine in solvent mixtures containing water and methanol, ethanol or isopropanol at 10-50° C. for 5-24 hours. The resulting intermediate is treated with an alkylating agent (R″″X where X represents bromo, iodo, alkylsulfonyloxy or arylsulfonyloxy) at 0-30° C. to give compounds Ic. In Step 7, compounds Ic are allowed to react with alkali metal alkoxide such as sodium methoxide or potassium ethoxide in the corresponding alkanol as solvent. This reaction is conveniently carried out at the reflux temperature of the alkanol for 1-24 hr.

In order to more fully illustrate the nature of the invention and the manner of practicing the same, the following experimental examples are presented.

EXAMPLE 1 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (I)

A stirred mixture of II (PCT/US94/08904, 3.37 g, 10.0 mmol) in dry dioxane (100 mL), under nitrogen was treated with Lawesson's Reagent (4.04 g, 10.0 mml), warmed to reflux during 1 h and refluxed for 1.5 h. The reaction was complete by TLC on silica gel with 10% MeOH-CHCl₃. It was kept at ambient temperature for 18 h and concentrated in vacuo. Chromatography of the residue on silica gel with mixtures of acetone-methylene chloride containing 10-15% acetone gave the product which was crystallized from acetone-hexane to give 1: mp 157.5-158.5° C.; HRMS theory for C₁₆H₂₀FN₃O₃S (M+): 353.1209; found: 353.1212. Anal. calcd for C₁₆H₂₀FN₃O₃S: C, 54.38; H, 5.38; N, 11.89; S, 9.07. Found: C, 54.21; H, 5.58; N 11.78; S, 8.93.

EXAMPLE 2 (S)-N-[[3-[3-Fluoro-4-[4- (5-methyl-1,3,4-thiadiazol-2-yl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (2)

According to Example 1, for the preparation of 1, 21 (PCT/US97/01970) was allowed to react with Lawesson's Reagent in refluxing dioxane to give 2: mp 222-223° C.; HRMS theory for C₁₉H₂₄FN₆O₂S₂ (M+H⁺): 451.1386; found 451.1381.

EXAMPLE 3 (S)-N-[[3-[3-Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidinie]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (3). STEP A: (S)-N-[[3-[3-Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (32).

A stirred suspension of 31 (WO95/25106, 0.349 g, 1.00 mmol) in 1:1 EtOH:H₂O (5 mL), under nitrogen, was treated with potassium cyanide (0.130 g, 2.00 mmol) and ammonium carbonate (0.701 g, 7.30 mmol), warmed at 55-60° C. for 5 h 15 min and kept at ambient temperature for 17 h 15 min. It was then chromatographed on silica gel with mixtures of MeOH-NH₄OH-CHCl₃ containing 5-20% MeOH and 0.5% NH₄OH to give 0.280 g of 32: HRMS calcd for C₁₉H₂₂FN₅O₅: 419.1605 (M⁺); found 419.1613; Anal. calcd for C₁₉H₂₂FN₅O₅•1 H₂O: C, 52.17; H, 5.53; N, 16.01. Found: C, 52.44; H, 5.30; N, 16.11.

STEP B: (S)-N-[[3-[3-Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (3).

A stirred suspension of 32 (0.210 g, 0.500 mmol) in dioxane (5.0 mL), under nitrogen was treated with Lawesson's Reagent (0.202 g, 0.500 mmol), refluxed for 4 h and concentrated in vacuo. The residue was chromatographed on silica gel with mixtures of MeOH-NH₄OH-CHCl₃ containing 1-10% MeOH and 0.1-0.5% NH₄OH and the resulting product was crystallized from MeOH-CHCl₃-EtOAc to give 0.0491 g of 3: mp 218.5° C.; HR FAB MS theory for C₁₉H₂₂FN₅O₄S (M⁺): 435.1376; found 435.1370. Anal. calcd for C₁₉H₂₂FN5O₄S•0.5 H₂O: C, 51.34; H, 5.21; N, 15.76. Found: C, 51.69; H, 5.00; N, 15.25.

EXAMPLE 4 (S)-N-[[3-[3-Fluoro4-(4-morpholinyl)phenyl]-2-oxo-5-oxazoidinyl]methyl]thioacetamide (4).

A solution of 41 (148 mg, 0.500 mmol) and 0.97 M KOH (0.515 mL) in absolute EtOH (5 mL) was added to a solution of ethyl dithioacetate (57 μL, 0.50 mmol) and sodium fluoride (20 mg, 0.47 mmol) in absolute EtOH (5 mL) and the mixture was kept at ambient temperature for 3 h 40 min. Additional ethyl dithioacetate (5 μL) was added after 1 h 55 min and additional 0.97 M KOH (40 mL) and sodium fluoride (6 mg) were added to the mixture after 3h 5 min. The reaction was followed by TLC on silica gel with 10% MeOH-CHCl₃ and 30% acetone-CH₂Cl₂. The major product had an R_(f) on TLC that was the same as that of 4.

EXAMPLE 5 S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea (5).

STEP A:

A solution of 51 (PCT/US94/08904, 2.07 g, 7.00 mmol) in CH₂Cl₂ was added, dropwise during 30 min, under nitrogen to an ice cold, stirred solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (1.95 g, 8.40 mmol) in CH₂Cl₂ (70 mL). The mixture was warmed slowly to ambient temperature and kept for 18 h. It was then diluted with CH₂Cl₂, washed with water and aqueous NaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 10% acetonitrile-CH₂Cl₂ gave 1.60 g of the isothiocyanate: HRMS theory for C₁₅H₁₆FN₃O₃S (M+): 337.0896; found 337.0888.

STEP B:

Anhydrous ammonia was bubbled for 7 min through a stirred solution of the product from Step I (1.00 g, 2.96 mmol) in THF (10 mL) and the mixture was kept at ambient temperature for 3 h 25 min and concentrated in vacuo. Crystallization of the residue from acetone-hexane gave 0.861 g of 5: mp 199-199.5° C.; MS m/z 354 (M⁺). Anal. calcd for C₁₅H₁₉FN₄O₃S: C, 50.84; H, 5.40; N, 15.81. Found: C, 50.87; H, 5.39; N, 15.72.

EXAMPLE 6 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea (6).

A stirred solution of methyl isothiocyanate (93 mg, 1.27 mmol) in THFP, was treated with 61 (295 mg, 1.00 mmol), kept at ambient temperature for 18 h and concentrated in vacuo. The residue was recrystallized from EtOAc-hexane to give 246 mg of 6: mp 158-160° C.; MS m/z 368 (M⁺). Anal. calcd for C₁₆H₂₁FN₄O₃S: C, 52.16; H. 5.74; N, 15.21. Found: C, 52.20; H. 5.85; N. 15.17.

EXAMPLE 7 (S)-cis-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

Step 1:

A mixture of (S)-(−)-N-[[3-[3-fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinylmethyl]acetamide S-oxide (4.50 g, can be obtained according to the procedures disclosed in International Publication No. WO 97/09328) and platinum oxide (697 mg) in methanol (164 mL) is shaken on the Parr apparatus under a hydrogen atmosphere at 40 psi for 18 hours. The catalyst is then removed by filtration through Celite, and the filtrate is concentrated under reduced pressure and the residue chromatographed on silica gel (230-400 mesh, 350 g), eluting with a gradient of methanol/methylene chloride (3/97-7/93). Pooling and concentration of those fractions with an R_(f)=0.44 by TLC (methanol/chloroform, 10/90) gives (S)-cis-(−)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, mp 203-204° C.

Step 2:

A mixture of the compound prepared in Step 1 (2.50 g) and hydroxylamine hydrochloride (2.36 g) in pyridine (30.6 mL) and ethanol (3.4 mL) is stirred in a screw-cap vial at 100° C. for 22 hrs and at ambient temperature for 16 hrs, during which additional hydroxylamine hydrochloride (944 mg) and pyridine (4 mL) is added. The reaction mixture is then concentrated under reduced pressure, diluted with saturated aqueous sodium bicarbonate (100 mL) and saline (50 mL), adjusted to pH 11 with solid sodium carbonate and extracted with methanol/methylene chloride (10/90, 5×100 mL). The combined organic phase is concentrated under reduced pressure, and the crude product is chromatographed on silica gel (230-400 mesh, 150 g), eluting with a gradient of methanol/methylene chloride (6/94-10/90). Pooling and concentration of those fractions with an R_(f)=0.14 by TLC (methanolchloroform, 10/90) gives (S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, mp 159-161° C.

Step 3:

A solution of ethyl dithioacetate (105 mL, 0.919 mmol) and sodium fluoride (39 mg, 0.919 mmol) in ethanol (9.2 mL) under a nitrogen atmosphere was treated with a mixture of (S)-cis-3-13-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Step 2,(300 mg, 0.919 mmol) and aqueous potassium hydroxide (1M, 0.92 mL) in ethanol (46 mL). The resulting solution was stirred at ambient temperature for 4 hours and was then diluted with methylene chloride (150 mL) and washed with water (50 mL), aqueous potassium hydrogen sulfate (1M, 50 mL) and brine (25 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo, and the crude product was triturated with methylene chloride/diethyl ether and filtered to give the title compound, mp 176-177° C. (dec.).

EXAMPLE 8 (S)-cis-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

Step 1:

A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (235 mg, 1.01 mmol) in anhydrous methylene chloride (10 mL) at 0° C. under a nitrogen atmosphere was treated with a solution of (S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Example 7, Step 2, (275 mg, 0.843 mmol) in anhydrous methylene chloride (34 mL) over 30 minutes. The resulting mixture was stirred at 0° C. for 30 minutes and at ambient temperature for 1 hour and was then diluted with methylene chloride (40 mL), washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was chromatographed on silica gel (70-230 mesh, 20 g), eluting with acetonitrile/methylene chloride (40/60), and those fractions with an R_(f)=0.07 by TLC (acetonitrile/methylene chloride, 30/70) were pooled and concentrated to give (S)-cis-3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone, mp 187-190° C. (dec.).

Step 2:

A solution of (S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone (Step 1, 290 mg, 0.787 mmol) in anhydrous tetrahydrofuran (39 mL) at 0° C. under a nitrogen atmosphere was treated (bubbled) with a stream of ammonia gas for 5 minutes. The reaction pot was sealed, and the resulting mixture was stirred at 0° C. for 1 hour. The excess ammonia was then removed under a stream of nitrogen, and the reaction mixture was concentrated in vacuo to give the crude product. Recrystallization from methanol/methylene chloride/diethyl ether gave the title compound, mp 206-208° C. (dec.).

EXAMPLE 9 (S)-trans-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-ylphenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

Step 1:

(S)-(−)-N-[[3-[3-fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-ox azolidinyl]methyl]acetamide S-oxide (disclosed in International Publication No. WO 97/09328) may be reduced to the corresponding cis- and trans-sulfoxides by catalytic hydrogenation in the presence of a catalyst and solvent. Alternatively, the sulfide by product of this reduction reaction can be oxidized with an oxidizing agent such NaIO₄ or meta-chloroperoxybenzoic acid in solvent to provide the cis- and trans-sulfoxides. Alternatively, the sulfide byproduct can be oxidized selectively to the trans isomer using t-butyl hydroperoxide and a catalyst such as Ti(OiPr)4 and D-diisopropyl tartrate in a suitable solvent. The isomeric mixture can then be separated by chromatography to isolate the trans-sulfoxide, mp 211-212° C. (dec.). A mixture of the trans-sulfoxide, (S)-trans-(−)-N-[[3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, (0.90 g) and hydroxylamine hydrochloride (0.85 g) in pyridine (11.0 mL) and ethanol (1.2 mL) is stirred in a screw-cap vial at 100° C. for 23 hrs and at ambient temperature for 19 hrs, during which additional hydroxylamine hydrochloride (340 mg) and pyridine (1 mL) is added. The reaction mixture is then concentrated under reduced pressure, diluted with saturated aqueous sodium carbonate (50 mL) and saline (50 mL) and extracted with methanol/methylene chloride (10/90, 6×100 mL). The combined organic phase is concentrated under reduced pressure, and the crude product is chromatographed on silica gel (230-400 mesh, 45 g), eluting with a gradient of methanol/methylene chloride (7.5/92.5-10/90). Pooling and concentration of those fractions with an R_(f)=0.14 by TLC (methanol/chloroform, 10/90) gives (S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, mp 138-140° C.

Step 2:

A solution of ethyl dithioacetate (105 mL, 0.919 mmol) and sodium fluoride (39 mg, 0.919 mmol) in ethanol (9.2 mL) under a nitrogen atmosphere was treated with a mixture of (S)-trans-3- [3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl-5-aminomethyl-2-oxazolidinone, as prepare in Step 1, (300 mg, 0.919 mmol) and aqueous potassium hydroxide (1M, 0.92 mL) in ethanol (46 mL). The resulting solution was stirred at ambient temperature for 17 hours and was then diluted with methylene chloride (150 mL), washed with water (2×50 mL) and brine (25 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was chromatographed on silica gel (230-400 mesh, 35 g), eluting with methanol/methylene chloride (3/97), and those fractions with an R_(f)=0.56 by TLC (methanolchloroform, 10/90) were pooled and concentrated and the residue recrystallized from methylene choride/diethyl ether to give the title compound, mp 193-194° C. (dec.).

EXAMPLE 10 (S)-trans-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

Step 1:

A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (192 mg, 0.827 mmol) in anhydrous methylene chloride (8.3 mL) at 0° C. under a nitrogen atmosphere was treated with a solution of (S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Example 9, Step 1, (225 mg, 0.689 mmol) in anhydrous methylene chloride (28 mL) over 30 minutes. The resulting mixture was stirred at 0° C. for 30 minutes and at ambient temperature for 40 minutes and was then diluted with methylene chloride (20 mL), washed with water (15 mL) and brine (15 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was chromatographed on silica gel (32-63 mm, 40 g), eluting with a gradient of acetonitrile/methylene chloride (30/70-60/40) under 15 psi N₂, and those fractions with an R_(f)=0.12 by TLC (acetonitrile/methylene chloride, 30/70) were pooled and concentrated to give (S′)-trans-3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone, mp 165-167° C.

Step 2:

A solution of (S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone (Step 1, 230 mg, 0.624 mmol) in anhydrous tetrahydrofuran (31.2 mL) at 0° C. under a nitrogen atmosphere was treated (bubbled) with a stream of ammonia gas for 5 minutes. The reaction pot was sealed, and the resulting mixture was stirred at 0° C. for 1 hour. The excess ammonia was then removed under a stream of nitrogen, and the reaction mixture was concentrated in vacuo to give the crude product. Trituration with methanol/methylene chloride/diethyl ether gave the title compound, mp 209-210° C. (dec.).

EXAMPLE 11 (S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

Step 1:

Starting with (S)-cis-(−)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-ylphenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide as prepared in Example 7, Step 1, and following the general procedure of Step 2, and making non-critical variations by substituting (S)-(−)-N-[[3-[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide S,S-dioxide (disclosed in International Publication No. WO 97/09328) for (S)-cis-(−)-N-[[3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, the product (S)-(−)-3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone is obtained, mp 194° C. (dec.).

Step 2:

A solution of ethyl dithioacetate (100 mL, 0.876 mmol) and sodium fluoride (37 mg, 0.876 mmol) in ethanol (8.8 mL) under a nitrogen atmosphere was treated with a mixture of (S)-(−)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Step 1, (300 mg, 0.876 mmol) and aqueous potassium hydroxide (1M, 0.88 mL) in ethanol (43.8 mL). The resulting mixture was stirred at ambient temperature for 26 hours, during which additional ethyl dithioacetate (50 mL, 0.438 mmol), sodium fluoride (19 mg, 0.438 mmol), aqueous potassium hydroxide (1M, 0.44 mL) and ethanol (3.0 mL) was added, and was then diluted with methylene chloride (150 mL), washed with water (50 mL), aqueous potassium hydrogen sulfate (1M, 50 mL) and brine (25 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was recrystallized from methylene chloride/diethyl ether to give the title compound, mp 186-187° C. (dec.).

EXAMPLE 12 (S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

Step 1:

A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (304 mg, 1.31 mmol) in anhydrous methylene chloride (13 mL) at 0° C. under a nitrogen atmosphere was treated with a solution of (S)-(−)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone, as prepared in Example 11, Step 1, (375 mg, 1.09 mmol) in anhydrous methylene chloride (88 mL) over 30 minutes. The resulting mixture was stirred at 0° C. for 30 minutes and at ambient temperature for 30 minutes and was then diluted with methylene chloride (40 mL), washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was chromatographed on silica gel (230-400 mesh, 45 g), eluting with acetonitrile/methylene chloride (7.5/92.5), and those fractions with an R_(f)=0.64 by TLC (acetonitrile/methylene chloride, 20/80) were pooled and concentrated to give (S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone, mp 158-162° C. (dec.).

Step 2:

A solution of (S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone (Step 1, 380 mg, 0.988 mmol) in anhydrous tetrahydrofuran (49 mL) at 0° C. under a nitrogen atmosphere was treated (bubbled) with a stream of ammonia gas for 5 minutes. The reaction pot was sealed, and the resulting mixture was stirred at 0° C. for 1 hour. The excess ammonia was then removed under a stream of nitrogen, and the reaction mixture was concentrated in vacuo to give the crude product. Recrystallization from methanol/methylene chloride/diethyl ether gave the title compound, mp 196-198° C. (dec.).

EXAMPLE 13 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazomidinyl]methyl]-thioformamide (7).

A stirred mixture of acetic anhydride (0.23 mL, 0.0024 mol) and 95-97% formic acid (0.10 mL, 0.0027 mL) was warmed, under nitrogen at 50-55° C. for 2 h, cooled to ambient temperature and treated, portionwise during 2 min, with 398 (0.45 g, 0.0015 mol). The suspension was kept at ambient temperature for 4 h and the resulting solution was treated with Et₂O (1 mL) and kept at ambient temperature for 18 h. The mixture was diluted with additional Et₂O (10 mL) and the solid was collected by filtration, washed with Et₂O and dried to give 0.38 g of 69: MS (ES) m/z 324 (M+H⁺), 346 (M+Na⁺); ¹H NMR (300 mHz, CDCl₃) d 3.08 (m, 4H), 3.72 (m, 2H), 3.77 (d,d, 1H), 3.89 (m, 4H), 4.04 (t, 1H), 4.80 (m, 1H), 6.33 (s, 1H), 7.05 (m, 2H), 7.45 (d,d, 1H), 8.27 (s, 1H).

A stirred mixture of 6 (0.38 g, 0.00118 mol) in dioxane (20 mL), under nitrogen was treated with 4 (0.51 g, 0.00126 mol), warmed to reflux during 30 min and kept at this temperature for 90 min. It was then evaporated under a stream of nitrogen. The residue was chromatographed on silica gel with 1.25% MeOH-CH₂Cl₂ and the slightly impure product was rechromatographed on silica gel with 25% EtOAc-CH₂Cl₂. The resulting product was crystallized from EtOAc-methyl tert-butyl ether to give 0.114 g of 7: mp 150-155° C. (dec); IR (DRIFT) 3322, 1752 cm⁻¹; MS(ES) m/z 340 (M+H⁺), 362 (M+Na⁺); ¹HNMR [300 MHz, (CD₃)₂SO] d 2.94 (m, 4H), 3.72 (m, 4H), 3.77 (d,d, 1H), 3.94 (t, 2H), 4.12 (t, 1H), 4.93 (m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d, 1H), 9.33 (d, 1H), 10.59 (s, 1H). Anal. calcd for C₁₆H₁₈FN₃O₃S: C, 53.08; H, 5.35; N, 12.38. Found: C, 53.02; H, 5.44; N, 12.36.

EXAMPLE 14 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiopropion-amide (9).

An ice cold, stirred solution of 39 (0.395 g, 0.00134 mol) and triethyl amine (0.186 mL, 0.0027 mol) in CH₂Cl₂ (20 mL), under nitrogen was treated, dropwise during 2 min, with a solution of propionyl chloride (0.128 mL, 0.00147 mol) in CH₂Cl₂ (3 mL). The mixture was kept in the ice bath for 20 min and at ambient temperature for 1 h. It was then diluted with CH₂Cl₂, washed with saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated. The residue (8) was used without further purification in the next reaction.

A stirred mixture of the product (8) from the previous reaction and dioxane (20 mL), under nitrogen, was treated, portionwise during 1 min, with Lawesson's reagent (0.58 g, 0.0014 mol) and refluxed for 2 h; it was then concentrated. The residue was chromatographed on silica gel with 2% MeOH-CHCl₃ and the product was crystallized from methyl tert-butyl ether to give 0.259 g of 9: mp 138-139° C.; MS(ES) m/z 368 (M+H⁺), 390 (M+Na⁺); IR (DRIFT) 3284, 3266, 1748, 1744 cm⁻¹; [α]²⁴ _(D)+20° (MeOH); 1H NMR[300 MHz, (CD₃)₂SO] d 1.12 (t, 3H), 2.56 (q, 2H), 2.94 (m, 4H), 3.72 (m, 4H), 3.78 (d,d, 1H), 3.90 (t, 2H), 4.11 (t, 1H), 4.93 (m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d, 1H), 10.30 (broad s, 1H). Anal. calcd for C₁₇H₂₂FN₃O₃S: C, 55.57; H, 6.03; N, 11.44. Found: C, 55.68; H, 6.21; N, 11.37.

EXAMPLE 15 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-chlorothioacetamide (11).

A stirred solution of 39 (1.54 g, 5.2 mmol) and triethylamine (750 mg, 7.5 mmol) in CH₂Cl₂ (50 mL), under nitrogen, was treated, dropwise, during 15 min with a solution of chloroacetyl chloride (465 mL, 5.8 mmol) in CH₂Cl₂ (30 mL) and kept at ambient temperature for 18 h. It was then washed with saturated NaHCO₃ and dilute NaCl, dried (Na₂SO₄) and concentrated. The residue was flash chromatographed on silica gel with 20-30% acetone-CH₂Cl₂ to give 1.49 g of 10⁹ which was used in the next reaction without further purification.

A stirred mixture of 10 (0.371 g, 1.0 mmol) and Lawesson's reagent (0.420 mg, 1.04 mmol) in dioxane (10 mL) was refluxed, under nitrogen for 2 h and concentrated under reduced pressure. The residue was chromatographed on silica gel with 3-10% acetone-CH₂Cl₂ to give 0.143 g of 11: MS (CI) m/z 388 (M+H⁺); ¹H NMR (300 MHz, CDCl₃) d 3.07 (m, 4H), 3.77 (d,d, 1H), 3.88 (m, 4H), 4.04 (m, 1H), 4.12 (t, 1H), 4.35 (m, 1H), 4.61 (s, 2H), 4.98 (m, 1H), 6.96 (t, 1H), 7.08 (d,d, 1H), 7.44 (d,d, 1H), 8.69 (s, 1H). Anal. calcd for C₁₆H₁₉ClFN₃O₃S: C, 49.55; H, 4.94; N, 10.83. Found: C, 49.38; H, 5.20; N, 10.27.

EXAMPLE 16 (S)-N-[[3-[3-Fluoro4-(4-moropholinyl)phenyl]-2-oxo-5-oxazolidinylmethyl]-α,α,α-trifluorothioacetamide (13).

An ice cold stirred solution of 39 (0.590 g, 2.0 mmol) and triethylamine (640 mL, 4.6 mmol) in CH₂Cl₂ (10 mL) was treated with trifluoroacetic anhydride (325 mL, 2.3 mmol) and kept in the ice bath for 10 min and then at ambient temperature. The reaction was followed by TLC on silica gel with 30% acetone-CH₂Cl₂. Additional trifluoroacetic anhydride and triethylamine were added after 3 d (64 mL/125 mL), 4 d (100 mL/220 mL) and 6 d (325 mL/1.0 mL). The reaction was complete 1 h after the last addition; it was mixed with CH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. The solid residue was recrystallized from acetone-heptane to give 0.566 g of 12: mp 161-164° C. (dec); MS(EI) m/z 391 (M⁺). Anal. calcd for C₁₆H₁₇F₄N₃O₄: C, 49.11; H, 4.38; N, 10.74. Found: C, 48.99; H, 4.56; N, 10.73.

A stirred mixture of 12 (0.391 g, 1.0 mmol) and Lawesson's reagent (0.422 g, 1.1 mmol) in dioxane (10 mL) was refluxed, under nitrogen for 2 h, cooled slowly to ambient temperature and concentrated in vacuo. The residue was flash chromatographed on silica gel with 5-15% acetone-CH₂Cl₂ and the product was crystallized from acetone-heptane to give 0.249 g of 13: mp 151-152° C.; MS(EI) m/z 407 (M⁺), 363, 209, 151, 95; ¹H NMR (300 Mz, CDCl₃) d 3.05 (m, 4H), 3.75, (d,d, 1H), 3.87 (m, 4H), 3.95 (m, 1H), 4.14 (t, 1H), 4.32 (m, 1H), 5.01 (m, 1H), 7.05 (d,d, 1H3, 7.38 (d,d, 1H), 9.03 (s, 1H). Anal. calcd for C₁₆H₁₇F₄N₃O₃S: C, 47.17; H, 4.21; N, 10.31. Found: C, 47.09; H, 4.35; N, 10.27.

EXAMPLE 17 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-fluorothioacetamide (15).

A stirred, ice cold solution of 39 (0.590 g, 2.0 mmol) and triethylamine (611 ml, 4.4 mmol) in CH₂Cl₂ (10 mL), under nitrogen, was treated, dropwise, with a solution of fluoroacetyl chloride (220 mL, 2.2 mmol) in CH₂Cl₂ (5 mL), kept in the ice bath for 10 min and at ambient temperature for 2 h. It was then diluted with CH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. The residue was chromatographed on silica gel with 10-30% acetone-CH₂Cl₂ to give 0.180 g of 14: MS(ES) m/z 356 (M+H⁺), 378 (M+Na⁺).

A solution of 14 (0.180 g, 0.507 mmol) in dioxane, under nitrogen, was treated with Lawesson's reagent (0.206 g, 0.51 mmol), warmed at 90-100° C. for 1 h and concentrated in vacuo. The residue was chromatographed on silica gel with 15%, acetone-CH₂Cl₂ to give 0.161 g of 15: MS(EI) m/z 371 (M⁺); ¹H NMR (300 MHz:, CDCl₃) d 3.05 (m, 4H), 3.78 (d,d, 1H), 3.87 (m, 4H), 4.03 (m, 1H), 4.11 (t, 1H), 4.38 (m, 1H), 4.98 (m, 1H), 5.07 (s, 1H), 5.23 (s, 1H), 6.93 (t, 1H), 7.08 (dd, 1H), 7.42 (d,d, 1H), 8.42 (s, 1H). Anal. calcd for C₁₆H₁₉F₂N₃O₃S: C, 51.74; H, 5.16; N, 11.31. Found: C, 51.79; H, 5.31; N, 11.02.

EXAMPLE 18 (S)-N[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α-difluorothioacetamide (17).

A stirred, ice cold mixture of 39 (0.590 g, 2.0 mmol), difluroacetic acid (190 mL, 2.0 mmol), and 1-hydroxybenzotriazole (0.297 g, 2.2 mmol) in DMF (5 mL) under nitrogen, was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.843 g, 4.4 mmol) and kept at ambient temperature for 18 h. It was diluted with CH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. The solid residue was crystallized form EtOAc-heptane to give 0.617 g of 16: mp 149-150° C.; ¹H NMR (300 MHz, CDCl3) d 3.05 (m, 4H), 3.66 (m, 2H), 3.85 (m, SH), 4.08 (t, 1H), 4.80 (m, 1H), 5.93 (t, J=53.9 Hz, 1H), 6.92 (t, 1H), 7.06 (m, 2H), 7.39 (d,d, 1H); MS(EI) m/z 373 (M⁺). Anal. calcd for C₁₆H₁₈F₃N₃O₄: C, 51.48; H, 4.86; N, 11.26. Found: C, 51.59; H, 4.91; N, 11.29.

A stirred solution of 16 (0.373 g, 1.00 mmol) in dioxane (10 mL), under nitrogen was treated with Lawesson's reagent (0.404 g, 1.00 mmol), warmed at about 95° C. ( for 1 h and concentrated in vacuo. Chromatography of the residue on silica gel with 10% acetone-CH₂Cl₂ and cyrstallization of the product from EtOAc-heptane gave 0.276 g of 17: mp 125-127° C.; MS(EI) m/z 389 (M⁺), 345, 305, 247, 209, 195, 151, 138, 123, 109, 95; ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.76 (d,d, 1H), 3.86 (m, 4H), 4.01 (m, 1H), 4.12 (t, 1H), 4.30 (m, 1H), 4.99 (m, 1H), 6.20 (t, J=55.9 Hz, 1H), 6.92 (t, 1H), 7.06 (d,d, 1H), 7.38 (d,d, 1H), 8.78 (broad s, 1H). Anal. calcd for C₁₆H₁₈F₃O₃S: C, 49.35; H, 4.66; N, 10.79. Found: C, 49.37; H, 4.71; N, 10.83.

EXAMPLE 19 (S)-N-[[3-[3-Fluoro4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-cyanothioacetamide (19).

An ice cold, stirred mixture of 39 (0.646 g, 2.19 mmol), cyanoacetic acid (0.179 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.351 g, 2.6 mmol) in DMF (5 mL), under nitrogen, was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.997 g, 5.2 mmol) and kept at ambient temperature for 24 h. It was diluted with CH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. The solid residue was crystallized from EtOAc-heptane to give 0.546 g of 18: mp 172-174° C.: IR (DRIFT) 3316, 2256, 1754, 1684 cm⁻¹; MS(EI) m/z 3132 (M⁺). Anal. calcd for C₁₇H₁₉FN₄O₄: C, 56.35; H, 5.28; N, 15.46. Found: C, 56.33; H, 5.30; N, 15.36.

A stirred solution of 18 (0.453 mg, 1.25 mmol) in dioxane (10 mL), under nitrogen, was treated with Lawesson's reagent (0.505 g, 1.25 mmol) and warmed at about 100° C. When the reaction was over (TLC with 30% acetone-CH₂Cl₂) the mixture was cooled and concentrated in vacuo. Chromatography of the residue on silica gel with 10-20% acetone-CH₂Cl₂ and crystallization of the product from EtOAc-heptane gave 0.110 g of 19: mp 186-187° C. (dec); MS(ES) m/z 379 (M+H⁺), 401 (M+Na⁺); ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.81 (d,d, 1H), 3.86 (m, 4H), 3.89 (s, 2H), 4.09 (t, 1H), 4.14 (m, 2H), 5.01 (m, 1H), 6.92 (t, 1H), 7.05 (d,d, 1H), 7.34 (d,d, 1H), 9.15 (s, 1H); IR (DRIFT) 3244, 2260, 1754 cm⁻¹. Anal. calcd for C₁₇H₁₉FN₄O₃S: C, 53.96; H, 5.06; N, 14.81. Found: C, 53.88; H, 5.39; N. 14.61.

EXAMPLE 20 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-2-oxo-5-oxazolidinyl]methyl]-α,α-dichlorothioacetamide (21).

A stirred, ice cold solution of 39 (0.885 g, 3.00 mmol) and triethylamine (975 mL, 7 mmol) in CH₂Cl₂ (15 mL), under nitrogen was treated, dropwise with a solution of dichloroacetic anhydride (555 mL, 3.5 mmol) in CH₂Cl₂ (5 mL) and kept in the ice bath for 15 min and at ambient temperature for 18 h. It was diluted with CH₂Cl₂, washed with water, saturated NaHCO₃ and dilute NaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 10% acetone-CH₂Cl₂ and crystallization of the product from acetone-heptane gave 0.463 g of 20: mp 197-198° C. (dec); MS(ES) m/z 406 (M+H⁺), 428 (M+Na⁺); 1H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.75 (m, 3H), 3.86 (m, 4H), 4.07 (t, 1H), 4.83 (m, 1H), 5.94 (s, 1H), 6.92 (t, 1H), 7.06 (m, 2H), 7.41 (d,d, 1H).

A stirred solution of 20 (0.305g, 0.75 mmol) in dioxane (5 ml), under nitrogen, was treated with Lawesson's reagent (0.202g, 0.5 mmol), warmed at about 90° C. for 1 hour, cooled and concentrated in vacuo. Chromatography of the residue on silica gel first with 30% acetone-heptane and then with 10% acetone-methylene chloride and crystallization of rh product form methylene chloride - heptane gave 0.203g with 21: mp 143-144° C.; HR17S (EI) calculated for C₁₆H₁₈cl₂ F N₃ 0₃ S(M) 421.0431. Anal. calcd for C₁₆H₁₈Cl₂F N₃O₃ S, C, 45.51; H, 4.30; N, 9.95. Found: C, 45.47; H, 4.24; H, 9.88.

EXAMPLE 21 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-(methoxycarbonyl)thioacetamide (23).

A stirred solution of 39 (0.955 g, 3.2 mmol) and triethylamine (650 mL, 4.5 mmol) in CH₂Cl₂ (50 mL), under nitrogen, was treated, dropwise during 15-20 min with a solution of methyl malonyl chloride (475 mL, 4.3 mmol) in CH₂Cl₂ (10 mL) and kept at ambient temperature for 3 days. It was then washed with water and dilute NaCl, dried and concentrated. The residue was flash chromatographed on silica gel with 15-30% acetone-CH₂Cl₂ and the product was crystallized form acetone-hexane to give 0.873 g of 22: mp 150-151° C.; ¹H NMR (300 MHz, CDCl3) d 3.03 (m, 4H), 3.34 (s, 2H), 3.67 (s, 3H), 3.69 (m, 2H), 3.76 (d,d, 1H), 3.85 (m, 4H), 4.00 (t, 1H), 4.78 (m, 1H), 6.90 (t, 1H), 7.06 (d,d, 1H), 7.41 (d,d, 1H), 7.57 (t, 1H); MS(ES) m/z 396 (M+H⁺), 418 (M+Na⁺); HRMS (FAB) calcd for C₁₈H₂₃FN₃O₆ (M+H⁺) 396.1571, found 396.1579. Anal. calcd for C₁₈H₂₂FN₃O₆: C, 54.68; H, 5.61; N, 10.63. Found: C, 54.69; H, 5.68; N, 10.58.

A stirred solution of 22 (0.395 g, 1.0 mmol) in dioxane (10 mL), under nitrogen, was treated with Lawesson's reagent (0.202 g, 0.5 mmol) and kept at ambient temperature for 4 h 10 min and at 80-90° C. for 1.5 h. The reaction was followed by TLC on silica gel with 10% MeOH-CHCl₃. At this time a new, less polar product had begun to form. It was kept at ambient temperature for 18 h and at 80° C. for 2 h; additional Laewsson's reagent (40 mg, 0.099 mmol) was added and warming at 80 ° C. was continued for 2 h; some starting material still remained. The mixture was concentrated and the residue was chromatographed on silica gel with 15% acetone-CH₂Cl₂ to give 0.348 g of 23: ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.71 (s, 3H), 3.81 (d,d, 1H), 3.86 (m, 4H), 3.88 (s, 2H), 4.07 (t, 1H), 4.19 (m, 2H), 4.99 (m, 1H), 6.91 (t, 1H), 7.07 (d,d, 1H), 7.42 (d,d, 1H), 9.52 (s, 1H); IR (DRIFT) 3269, 1743 cm⁻¹; MS(EI) m/z 411 (M⁺). Anal. calcd for C₁₈H₂₂FN₃O₅S: C, 52.54; H, 5.39; N, 10.21. Found: C, 52.58; H, 5.43; N, 10.14.

EXAMPLE 22 (S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (25).

A stirred mixture of 24 (0.150 g, 0.470 mmol) and dioxane (12.5 mL), under nitrogen, was treated with Lawesson's reagent (0.20 g, 0.50 mmol), refluxed for 1.5 h, kept at ambient temperature for 18 h and concentrated in vacuo. Flash chromatography of the residue on silica gel with 5% MeOH-CHCl₃ gave the product which was crystallized from MeOH to give 0.100 g (63.4%) of 25: mp 161-163° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.43 (s, 3H), 3.87 (m, 3H), 4.22 (t, 1H), 4.99 (m, 1H), 7.51 (d, 1H), 7.77 (m, 2H), 8.26 (s, 1H), 8.97 (d, 1H), 10.35 (broad s, 1H); IR (mull) 3259, 3226, 3044, 1752 cm⁻¹; MS(ES) m/z 336 (M+H⁺), 358 (M+Na⁺). Anal. calcd for C₁₄H₁₄FN₅O₂S: C, 50.14; H, 4.21; N, 20.88. Found: C, 50.18; H, 4.26;

EXAMPLE 23 (S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (25).

A stirred mixture of 26 (0.26 g, 0.938 mmol), ethyl dithioacetate (0.12 g, 0.998 mmol), sodium fluoride (0.040 g, 0.953 mmol) and absolute EtOH (10 mL), under nitrogen, was treated during 5 min with a solution of 0.97 M KOH (1.03 mL) in EtOH and kept at ambient temperature for 2 h. It was then diluted with CH₂Cl₂ (75mL), washed with water, 1M KHSO₄, water and brine and evaporated. The residue was flash chromatographed on silica gel with 5% MeOH-CHCl₃ and the product was crystallized from MeOH to give 0.118 g, mp 164-165° C. (dec) and 0.026 g, mp 162-163° C. (dec) of 25.

EXAMPLE 24 (S)-N-[[3-[1-(Hydroxyacetyl)-5-indolnyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (28).

A stirred, ice cold solution of 52 (8.80 g, 0.0240 mol) in CH₂Cl₂ (25 mL) was treated during 20 min with a solution of trifluoroacetic acid (25 mL) in CH₂Cl₂ (10 mL). The mixture was kept in the ice bath for 2 h 15 min and concentrated under reduced pressure. A solution of the residue in CH₂Cl₂ was washed with saturated NaHCO₃ and dilute NaCl, dried (Na₂SO₄) and concentrated. The residue was used in the next reaction without further purification. A sample of this material (53) had: ¹H NMR (300 MHz, CDCl₃) d 3.00 (t, 2H), 3.54 (t, 2H), 3.85 (broad s, 1H), 5.17 (s, 2H), 6.59 (d, 1H), 6.66 (broad s, 1H), 6.91 (d, 1H), 7.23 (s, 1H), 7.36 (m, 5H); MS m/z 269 (M+H⁺).

An ice cold, stirred mixture of 53 (crude product from the previous reaction), acetone (200 mL), saturated NaHCO₃ (200 mL) and water (30 mL) was treated, dropwise during 20 min, with a solution of benzyloxyacetyl chloride (4.70 mL, 0.030 mol) in acetone (55 mL), warmed slowly to ambient temperature and kept for 18 h. Additional benzyloxytacetyl chloride (1.0 mL) in acetone 35 mL) was added dropwise and the mixture was kept at ambient temperature for an additional 3 h and diluted with EtOAc and water. A solid was collected by filtration and dried to give 4.00 g of crude product. The EtOAc solution was dried (Na₂SO₄) and concentrated to give 5.36 g of additional crude product. Crystallization of the product from EtOAc gave a total of 6.35 g of 5414, mp 157-159.5° C. The analytical sample had: mp 158-159.5° C.; ¹H NMR (300 MHz, CDCl₃) δ 3,16 (t,2H), 4.01(t,2H), 4.21 (s, 2H), 4.69 (8, 2H), 5.19 (s, 2H), 6.67 (s, 1H), 6.97 (d, 1H), 7.36 (m, 10H), 7.50 (broad s, 1H), 8.15 (d, 1H); MS(EI) m/z (relative intensity) 416 (M⁺, 9), 310 (8), 202 (10), 133 (8), 92 (8), 91 (99), 79 (7), 77 (9), 65 (12), 51 (6); IR (mull) 2381, 1722, 1659, 1608, 1558 cm⁻¹. Anal. calcd for C₂₅H₂₄N₂O₄: C, 72.10; H, 5.81; N, 6.73. Found: C, 72.05; H, 5.86; N, 6.68.

A stirred suspension of 54 (1.16 g, 2.78 mmol) in THF (42 mL) was cooled, under nitrogen, to −78° C. and treated, dropwise, during 5 min with 1.6 M n-BuLi in hexane (1.83 mL). It was kept at −78° C. for 50 min, treated, dropwise, during 5 min with a solution of (R)-(−)-glycidyl butyrate (0.500 g, 3.47 mmol) in THF (2 mL), allowed to warm to ambient temperature during 3 h and kept for 18 h. It was then diluted with EtOAc, washed with saturated NH₄Cl, water and brine, dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel with 3% MeOH-0.2% NH₄OH-CHCl₃ gave 0.60 g (56%) of 5514: ¹H NMR 1300 MHz, (CD₃)₂SO] δ 3.14 (t, 2H), 3.59 (m, 2H), 3.79 (d,d, 1H), 4.03 (m, 3H), 4.29 (s, 2H), 4.58 (s, 2H), 4.65 (m, 1H), 5.20 (t, 1H), 7.31 (m, 6H), 7.55 (s, 1H), 8.03 (d, 1H); MS(ES) m/z 383 (M+H⁺), 405 (M+Na⁺).

An ice cold, stirred mixture of 55 (0.60 g, 1.57 mmol), triethylamine (2.2 mL), and CH₂Cl₂ (12 mL), under nitrogen, was treated with 3-nitrobenzenesulfonyl chloride (0.44 g, 1.99 mmol) and kept in the ice bath for 30 min and at ambient temperature for 60 min. It was then diluted with CH₂Cl₂, washed with water and brine, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 15% CH₃CN-CH₂Cl₂ gave 0.70 g of 56: ¹H NMR (300 MHz, CDCl₃) d 3.19 (t, J=8.3 Hz, 2H), 3.88 (d,d, 1H), 4.04 (t, J=8.4 Hz, 2H), 4.14 (t, 1H), 4.23 (s, 2H), 4.42 (m, 2H) 4.70 (s, 2H), 4.84 (m, 1H), 6.97 (m, 1H), 7.34 (m, 5H), 7.58 (s, 1H), 7.81 (t, 1H), 8.22 (m, 2H), 8.53 (m, 1H), 8.73 (m, 1H); MS(ES) m/z 568 (M+H⁺), 590 (M+Na⁺).

A stirred mixture of 56 (crude product from 0.00314 mol of 55), acetonitride (70 mL), isopropanol (70 mL) and 29% ammonium hydroxide (70 mL) was warmed at 40-44° C. for 7h and kept at ambient temperature for 18 h. It was concentrated in vacuo to an aqueous residue with was extracted with CH₂Cl₂. The extract was washed with water and brine, dried (Na2SO₄) and concentrated. Chromatography of the residue on silica gel with 8% MeOH-0.5% NH₄OH-CHCl₃ gave 1.05 g of 57: ¹H NMR [300 MHz, (CD₃)₂SO] d 2.78 (m, 2H), 3.13 (t, 2H), 3.82 (d,d, 1H), 4.01 (m, 3H), 4.29 (s, 2H), 4.58 (s, 2H), 4.58 (m, 1H), 7.31 (m, 6H), 7.54 (broad s, 1H), 8.03 (d, 1H); MS(ES) m/z 382 (M+H⁺), 404 (M+Na⁺).

A mixture of 57 (0.46 g, 1.21 mmol), MeOH (150 mL), 1 M HCI (1.2 mL) and 5% palladium-on-carbon catalyst (250 mg) was hydrogenated at an initial pressure of 49 psi for 5 h. Additional 1M HCl (0.5 mL) and catalyst (100 mg) were added and hydrogenation was continued for 18 h. The catalyst was removed by filtration and the filtrate was concentrated to give 0.34 g of 27: ¹H NMR [300 MHz, (CD₃)₂SO] δ 3.15 (t, 2H), 3.22 (broad s, 2H), 3.84 (d,d, 1H), 4.00 (t, 2H), 4.15 (s, 2H), 4.15 (m, 1H), 4.92 (m, 1H), 7.24 (q, 1H), 7.50 (d, 1H), 8.03 (d, 1H), 8.37 (broad s, 3H); MS(ES) m/z 2.92 (M+H⁺).

A suspension of 27 (0.10 g, 0.34 mmol) in a mixture of EtOH (15 mL) and 0.97 M KOH (0.7 mL) was added, under nitrogen to a stirred mixture of ethyl dithioacetate (0.0412 g, 0.343 mmol) and sodium fluoride (0.0137 g, 0.326 mmol) in EtOH (5 mL) and the mixture was kept at ambient temperature for 2h 15 min. Additional 0.97 M KOH (0.2 mL), sodium iodide (6 mg) and ethyl dithioacetate (20 mg) were added and the mixture was stirred for 2 h, mixed with CH₂Cl₂ (150 mL), washed with water, 1M KHSO₄ and brine, dried (Na₂SO₄) and concentrated. The residue was crystallized from acetone to give 0.0404 g of 28: mp 175-176° C. (dec); MS (FAB) m/z 350 (M+H⁺), 349 (M⁺), 331, 316, 205, 73; HR MS (FAB) calcd for C₁₆H₂₀N₃O₄S (M+H⁺) 350.1174, found 350.1183; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 3.14 (t, 2H), 3.79 (d,d, 1H), 3.89 (t, 2H), 4.00 (t, 2H), 4.12 (m, 3H), 4.83 (t, 1H), 4.90 (m, 1H), 7.25 (d, 1H), 7.50 (s, 1H), 8.03 (d, 1H), 10.35 (s, 1H); IR (DRIFT) 3255, 3223, 3068, 1747, 1639, 1614 cm⁻¹.

EXAMPLE 25 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (30).

A mixture of 58 (3.00 g, 7.00 mmol), TBF (60 mL), absolute EtOH (100 mL) and 10% palladium-on-carbon catalyst (415 mg) was hydrogenated at an initial pressure of 58 psi for 2 h 50 min. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to give 2.67 g of 59 which was used without further purification in the next reaction: ¹H NMR (300 MHz, CDCl₃) d 2.16 (broad s), 3.02 (m, 8H), 3.73 (d,d, J=3.9, 12.6 Hz, 1H), 3.96 (m, 3H), 4.72 (m, 1H), 6.92 (t, J=9.2 Hz, 1H), 7.11 (m, 1H), 7.43 (d,d, J=2.6, 14.3 Hz, 1H); MS(ES) m/z 296 (M+H⁺).

A stirred, ice cold mixture of 59 (2.67 g from the previous reaction), acetone (:L90 mL) and saturated NaHCO₃ (70 mL) was treated, dropwise during 2-3 min with a 30 solution of benzyloxyacetyl chloride (1.34 mL, 8.61 mmol) in acetone (25 mL), kept in the ice bath for 1 h and diluted with EtOAc. The aqueous layer was extracted with EtOAc and the combined organic solution was washed with dilute NaCl, dried and concentrated. Chromatography of the residue on silica gel with 30% acetone CH₂Cl₂ gave 2.64 g of 60: ¹H NMR (300 MHz, CDCl₃) d 2.28 (broad s, 1H), 3.00 (m, 4H), 3.66 (m, 2H), 3.77 (m, 3H), 3.96 (m, 3H), 4.22 (s, 2H), 4.61 (s, 2H), 4.74 (m, 1H), 6.88 (t, J=9.2 Hz, 1H), 7.12 (m, 1H), 7.35 (s, 5H), 7.46 (d,d, J=2.6, 14.2 Hz, 1H); IR (mull) 3406, 1748, 1647 cm⁻¹; HRMS(EI) calcd for C₂₃H₂₆FN₃O₅ (M+) 443.1856, found 443.1842.

A stirred, ice cold mixture of 60 (2.64 g, 6.00 mmol) and triethylamine (1.14 mL, 8.16 mmol) in CH₂Cl₂ (200 mL), under nitrogen, was treated with 3-nitrobenzenesulfonyl chloride (1.78 g, 8.04 mmol), warmed to ambient temperature and kept for 5 h 20 min. Additional 3-nitrobenzenesulfonyl chloride (180 mg) and triethylamine (0.20 mL) were added and the mixture was kept at ambient temperature for 18 h, diluted with CH₂Cl₂ and washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 40-60% acetone-hexane gave 3.36 g of 77: ¹H NMR (300 MHz, CDCl₃) d 3.02 (broad s, 4H), 3.66 (broad s, 2H), 3.78 (broad s, 2H), 3.87 (d,d, J=5.9, 9.1 Hz, 1H), 4.09 (t, J=9.2 Hz, 1H), 4.22 (s, 2H), 4.41 (m, 2H), 4.61 (s, 2H), 4.84 (m, 1H), 6.88 (t, J=9.1 Hz, 1H), 7.02 (m, 1H), 7.35 (m, 6H), 7.82 (t, J=8.0 Hz, 1H), 8.23 (m, 1H), 8.53 (m, 1H), 8.73 (m, 1H); MS(ES) m/z 629 (M+H⁺).

A solution of 77 (3.36 g, 5.34 mmol) in a mixture of acetonitrile (90 mL), isopropanol (90 mL) and concentrated ammonium hydroxide (90 mL) was warmed at 40-45° C. for 18 h, treated with additional ammonium hydroxide (30 mL), warmed at 410-45° C. for 8 h, treated with additional ammonium hydroxide (25 mL) and warmed at 45° C. for 18 h. It was then mixed with water and extracted with CH₂Cl₂. The extract was washed with dilute NaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 5% MeOH-0.5% NH₄OH-CHCl₃ gave 2.44 g of 61: ¹H NMR (300 MHz, CDCl₃) d 1.50 (broad s), 3.04 (m, 6H), 3.65 (broad s, 2H), 3.81 (m, 3H), 3.99 (t, 1H), 4.21 (s, 2H), 4.61 (s, 2H), 4.66 (m, 1H), 6.88 (t, 1H), 7.12 (m, 1H), 7.33 (m, 5H), 7.47 (d,d, 1H); MS(ES) m/z 443 (M+H⁺).

A solution of 61 (1.45 g, 3.3 mmol) and 1.0 N HCl (3.65 mL) in 95% EtOH (150 mL) was treated with 5% palladium-on-carbon catalyst (500 mg) and hydrogenated at an initial pressure of 54 psi for 20 h 15 min. Additional 1.0 N HCI (0.5 mL) and catalyst (100 mg) were added and hydrogenation was continued for 20 h 30 min at an initial pressure of 60 psi. The reaction was compete by TLC; it was neutralized with concentrated NH₄OH, filtered and concentrated in vacuo to give 1.18 g of 29: ¹H NMR [300 MHz, (CD₃)₂SO] d 2.94 (broad s, 4H), 3.19 (m, 2H), 3.48 (broad s, 2H), 3.60 (broad s, 2H), 3.84 (m, 1H), 4.14 (m, 3H), 4.66 (broad s, 1H), 4.93 (m, 1H), 7.07 (t, 1H), 7.16 (d,d, 1H), 7.48 (d,d, 1H), 8.04 (broad s); IR (mull) 3420, 3099, 3040, 3008, 1755, 1641 cm⁻¹; MS(ES) m/z 353 (M+H⁺). Anal. calcd for C₁₆H₂₂ClFN₄O₄: C, 49.42; H, 5.70; Cl, 9.12; N, 14.41. Found: C, 48.16; H, 5.82; Cl, 10.00; N, 14.28.

A stirred mixture of ethyl dithioacetate (180 mL, 1.56 mmol), sodium fluoride (72 mg, 1.7 mmol), 29 (500 mg, 1.29 mmol) and EtOH (70 mL) under nitrogen, was treated with 0.97M KOH (1.46 mL, 1.42 mmol) and the resulting solution was kept at ambient temperature for 3 h 35 min, diluted with CHCl₃, washed with water and dilute NaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 5% MeOH-0.5% NH₄OH-CHCl₃ and crystallization of the resulting product from absolute EtOH gave 0.238 mg (44.9%) 30: mp 163-165° C.; ¹H NMR (300 MHz, CDCl₃) d 2.60 (s, 3H), 3.06 (m, 4H), 3.45 (m, 2H), 3.61 (m, 1H), 3.82 (m, 3H), 4.07 (m, 2H), 4.25 (m, 3H), 4.97 (m, 1H), 6.91 (t, 1H), 7.07 (m, 1H), 7.45 (d,d, 1H), 7.91 (broad s, 1H); MS(FAB) m/z (relative intensity) 411 (M+H⁺, 100), 410 (M⁺, 66.5), 266 (3.1); IR 3292, 1733, 1653 cm⁻¹. Anal. calcd for C₁₈H₂₃FN₄O₄S: C, 52.67; H, 5.65; N, 13.65. Found: C, 52.76; H, 5.58; N, 13.64.

EXAMPLE 26 (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide (32).

An ice cold, stirred mixture of 31 (0.38 g, 0.0012 mol) and triethylamine (0.38 mL, 0.0027 mol) in THF (12 mL), under nitrogen, was treated with ethyl dithioacetate (0.16 mL, 0.0014 mol) and then kept at ambient temperature for 24.5 h and concentrated in vacuo. A solution of the residue in CH₂Cl₂ was washed with saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated. Crystallization of the residue from EtOAc-hexane gave 0.355 g of 32: mp 155-156° C.; MS(ES) m/z 370 (M+H⁺), 392 (M+Na⁺); IR (DRIFT) 3206, 3042, 1759, 1738 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) d 2.60 (s, 3H), 2.95 (s, 4H), 3.43 (m, 4H), 3.82 (d, d, 1H), 4.08 (m, 2H), 4.27 (m, 1H), 4.98 (m, 1H), 7.06 (m, 1H), 7.33 (broad S, 1H), 7.51 (d, 1H), 8.03 (broad s, 1H). Anal. calcd for C₁₆H₂₀FN₃O₂S₂: C, 52.01; H, 5.46; N, 11.37. Found: C, 51.86; H, 5.43; N, 11.20.

EXAMPLE 27 (S)-[[3-[3-Fluoro- (4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide, thiomorpholine S-oxide (34).

An ice cold, stirred mixture of sodium metaperiodate (1.08 g, 5.05 mmol) and water (12 mL), under nitrogen, was treated with 62 (1.5 g, 4.8 mmol) and MeOH (17 mL) and kept at 6° C. for 18 h and at 4° C. for 3 h. It was then treated with additional sodium metaperiodate (0.1 g), kept at 4° C. for 3 h and extracted with CHCl₃. The extract was dried (MgSO₄) and concentrated to give 1.4 g of 63: ¹H NMR [300 MHz, (CD₃)₂SO] d 2.84 (m, 2H), 3.01 (m, 2H), 3.16 (m, 2H), 3.50 (m, 3H), 3.65 (m, 1H), 3.77 (d,d, 1H), 4.03 (t, 1H), 4.66 (m, 1H), 5.18 (t, 1H), 7.16 (m, 2H), 7.52 (m, 1H), MS(ES) m/z 329 (M+H⁺), 351 (M+Na⁺).

An ice cold, stirred mixture of 63 (1.27 g, 3.87 mmol) and triethylamine (0.732 mL, 5.25 mmol) in CH2Cl₂ (130 mL), under nitrogen, was treated with m-nitrobenzenesulfonyl chloride (1.15 g, 5.19 mmol) and kept at ambient temperature for about 24 h. It was diluted with CH₂Cl₂, washed with water and brine, dried (Na₂SO₄) and concentrated to give 78 which was used in the next reaction without purification.

A stirred mixture of the product (78) from the previous reaction, acetonitrile (70 mL) and isopropanol (70 mL) was treated with concentrated ammonium hydroxide (70 mL, 29.9% NH3) and kept at 40° C. for 2 h, at ambient temperature for 18 h and at 40-45 ° C. for 4 h; it was concentrated to about 50 mL, diluted with water and extracted with CH₂Cl₂. The extracts were washed with water and brine, dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel with 5% MeOH-CHCl₃ gave 0.58 g of 33: MS(ES) m/z 328 (M+H⁺), 350 (M+Na⁺); ¹H NMR [300 MHz, (CD₃)₂SO] d 2.81 (m, 4H), 3.01 (m, 2H), 3.16 (m, 2H), 3.30 (broad s), 3.49 (m, 2H), 3.80 (d,d, 1H), 4.01 (t, 1H), 4.58 (m, 1H), 7.19 (m, 2H), 7.51 (m, 1H).

A stirred suspension of 33 (3.7 g, 0.011 mol) and triethylamine (3.5 mL, 0.025 mol) in THF (120 mL) was cooled, in an ice bath, under nitrogen, treated, dropwise during 2 min, with a solution of ethyl dithioacetate (1.47 mL, 0.0128 mol) in THF (2 mL) and kept at ambient temperature for 22 h. The resulting solution was concentrated and the residue crystallized from acetonitrile to give 3.61 g of 34: mp 176-177° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 2.85 (m, 2H), 3.01 (m, 2H), 3.18 (m, 3H), 3.50 (m, 2H), 3.78 (d,d, 1H), 3.89 (broad s, 2H), 4.12 (t, 1H), 4.92 (m, 1H), 7.18 (m, 2H), 7.49 (m, 1H), 10.33 (s, 1H); IR (DRIFT) 3186, 3102, 1741 cm⁻¹; MS(ES) m/z 386 (M+H⁺), 408 (M+Na⁺). Anal. calcd for C₁₆H₂₀FN₃O₃S₂•0.5 H₂O: C, 48.71; H, 5.37; N, 10.65; S, 16.26; H₂0, 2.38. Found: C, 48.75; H, 5.17; N, 10.72: S, 16.07; H₂O, 1.72.

EXAMPLE 28 (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide, thiomorpholine S, S-dioxide (36).

A stirred mixture of 62 (0.399 g, 0.00128 mol) in 25% water/acetone (12 mL), under nitrogen was treated with N-methylmorpholine, N-oxide (0.45 g, 0.00384 mol) and 0.1 mL of a 2.5 wt % solution of osmium tetroxide in tert-butanol. It was kept at ambient temperature for 18 h, mixed with saturated NaHSO₃ (50 mL) and extracted with CH₂Cl₂. The extract was washed with saturated NaHSO₃ and brine, dried (Na₂SO₄) and concentrated. The residue was mixed with 3.5% MeOH-CH₂Cl₂ and filtered; the solid was dissolved in 15% MeOH-CH₂Cl₂ and concentrated to give 0.29 g of 64. The filtrate was chromatographed on silica gel with 3.5% MeOH-CH₂Cl₂ to give 0.1 of additional 64: MS(ES) m/z 345 (M+H⁺), 367 (M+Na⁺); ¹H NMR [300 MHz, (CD₃)₂SO] d 3.26 (m, 4H), 3.44 (m, 4H), 3.60 (m, 2H), 3.80 (d,d, 1H), 4.05 (t, 1H), 4.69 (m, 1H), 7.22 (m, 2H), 7.54 (d, 1H).

A stirred mixture of 64 (0.39 g, 0.00113 mol) and triethylamine (0.214 mL, 0.00154 mol) in CH₂Cl₂ (37 mL) was cooled, under nitrogen, in an ice bath and treated, portionwise during 5 min, with 3-nitrobenzenesulfonyl chloride (0.335 g, 0.00151 mol). The mixture was kept in the ice bath for 20 min and at ambient temperature for 18 h and concentrated in vacuo. A stirred solution of the residue in 2-propanol (25 mL) and acetonitrile (25 mL), under nitrogen, was treated with 30% NH₄OH (25 mL), warmed at 50-55° C. for 6 h and kept at ambient temperature for 48 h. It was concentrated to remove the organic solvents, diluted with water and extracted with CH₂Cl₂. The extract was washed with water and brine, dried (MgSO₄) and concentrated. Flash chromatography of the residue on silica gel with 6% MeOH-0.4% NH₄OH-CHCl₃ gave 0.29 g of 35: ¹H NMR [300 MHz, (CD₃)₂SO] d 1.59 (broad s, 2H), 2.78 (m, 2H), 3.24 (m, 4H), 3.43 (m, 4H), 3.81 (d,d, 1H), 4.01 (t, 1H), 4.57 (m, 1H), 7.18 (m, 2H), 7.52 (m, 1H); MS(ES) m/z 344 (M+H⁺), 366 (M+Na⁺).

A stirred, ice cold suspension of 35 (0.28 g, 0.85 mmol) in a mixture of Et₃N (0.26 mL, 1.9 mmol) and THF (10 mL) was treated with ethyl dithioacetate (0.11 mL, about 6 drops) and kept in the ice bath for 20 min and then at ambient temperature; the reaction was followed by TLC. After 20 h there was still a suspension and only partial reaction; additional THF (10 mL) and ethyl dithioacetate (3 drops) were added. After an additional 48 h the reaction was still incomplete; the suspension was treated with CH₂Cl₂ (10 mL) and kept for 72 h. At this time almost complete solution and an almost complete conversion to product had been obtained. An additional drop of ethyl dithioacetate was added and the mixture was kept at ambient temperature for 5 d and concentrated in vacuo. The residue was miffed with EtOAc, washed with saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated. Crystallization of the residue from MeOH-EtOAc gave 0.209 g of 36: mp 197-198° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 3.24 (m, 4H), 3.43 (m, 4H), 3.78 (d,d, 1H), 3.88 (m, 2H), 4.12 (t, 1H), 4.92 (m, 1H), 7.18 (m, 2H), 7.50 (m, 1H), 10.37 (broad s, 1H); IR (mull) 3300, 3267, 1743 cm⁻¹; MS(ES) m/z 424 (M+Na⁺). Anal. calcd for C₁₆H₂₀FN₃O₄S₂: C, 47.87; H, 5.02; N, 10.47. Found: C, 47.84; H, 5.23; N, 10.28.

EXAMPLE 29 (S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide (38).

A stirred mixture of 65 (1.8 g, 0.00396 mol), pyridine (30 mL) and absolute EtOH (3 mL), under nitrogen, was treated with hydroxylamine hydrochloride (1.44 g, 0.0207 mol), warmed to the reflux temperature during 2 h, refluxed for 3.5 h, kept at ambient temperature for 18 h and at reflux for 4 h. It was concentrated in vacuo and the residue was mixed with water, adjusted to pH 11 with saturated NaHCO₃ and extracted with Et₂O. The extracts were washed with brine, dried (Na₂SO₄) and concentrated. Chromatography of the residue on silica gel with 5% MeOH-0.35% NH₄OH-CHCl₃ gave 0.75 g of recovered 65 and 0.72 g of 66: ¹H NMR [300 MHz, (CD₃)₂SO] d 1.40 (s, 9H), 1.72 (broad s, 2H), 2.78 (m, 2H), 2.97 (m, 4H), 3.80 (d,d, 1H), 4.00 (t, 1H), 4.59 (m, 1H), 7.27 (d, 2H); MS(ES) m/z 413 (M+H⁺), 435 (M+Na⁺).

An ice cold, stirred mixture of 66 (0.75 g, 0.0018 mol) and triethylamine (0.315 mL, 0.00225 mol) in THF (12 mL), under nitrogen, was treated, dropwise with benzyl chloroformate (0.29 mL, 0.0020 mol), kept in the ice bath for 15 min and at ambient temperature for 2 h and concentrated in vacuo. The residue was mixed with CH₂Cl₂ and washed with saturated NaHCO₃, water and brine, dried (Na₂SO₄) and concentrated. This residue was mixed with Et₂O and filtered to give 0.939 g of 67: mp 116-118° C.; ¹H NMR (300 MHz, CDCl₃) d 1.48 (s, 9H), 3.08 (m, 4H), 3.53 (m, 4H), 3.60 (m, 2H), 3.73 (m, 1H), 3.96 (t, 1H), 4.76 (m, 1H), 5.10 (s, 2H), 5.21 (m, 1H),7.07 (d, 2H), 7.31 (s, 5H); MS(ES) m/z 547 (M+H⁺), 569 (M+Na⁺).

Compound 67 (0.805 g, 0.00147 mol) was added with stirring, portionwise during 5 min, under nitrogen, to ice cold trifluoroacetic acid (9 mL). The resulting solution was kept in the ice bath for 1 h and then concentrated under a stream of nitrogen. The residue was mixed with ice and saturated NaHCO₃ and extracted with CH₂Cl₂; the extract was washed with water and brine, dried (Na2SO₄) and concentrated to give 0.63 g of product. The combined aqueous layer was reextracted with EtOAc; the extracts were washed with water and brine, dried (Na₂SO₄) and concentrated to give additional product. The combined product amounted to 0.68 g of 68 which was used in the next reaction without further purification.

An ice cold, stirred mixture of 68 (0.68 g, 0.00152 mol), saturated NaHCO₃ (15.2 mL) and acetone (40 mL), under nitrogen was treated, dropwise during 15 min, with a solution of benzyloxyacetyl chloride (0.29 mL, 0.0019 mol) in acetone (5 mL), kept at ambient temperature for 6 h, diluted with EtOAc and washed with water and brine. The extract was dried (MgSO₄) and concentrated in vacuo to give 0.72 g of 69: MS(ES) m/z 395 (M+H⁺), 617 (M+Na⁺); ¹H NMR (300 MHz, CDCl₃) d 3.12 (m, 4H), 3.59 (m, 4H), 3.74 (m, 3H), 3.96 (t, 1H), 4.22 (s, 2H), 4.62 (s, 2H), 4.75 (broad s, 1H), 5.10 (s, 2H), 5.22 (m, 1H), 7.08 (d, 2H), 7.33 (m, 10H).

A mixture of 69 (0.72 g, 0.0012 mol), MeOH and 5% palladium-on-carbon catalyst (0.4 g) was hydrogenated at an initial pressure of 45 psi for 4 h. By TLC (8% MeOH-0.5% NH₄OH-CHCl₃) the starting material had been reduced and two products formed. 1M Hydrochloric acid (1.34 mL) was added and hydrogenation was continued at an initial pressure of 40 psi for 21 h. By TLC only the more polar product remained. The catalyst was removed by filtration and the filtrate was concentrated to give 0.40 g of 37: MS(ES) m/z 371 (M+H⁺), 393 (M+Na⁺); ¹H NMR [300 MHz, (CD₃)₂SO] d 3.02 (s, 4H), 3.20 (m, 2H), 3.43 (s, 2H), 3.56 (s, 2H), 3.84 (m, 1H), 3.84 (broad s), 4.10 (s, 2H), 4.14 (t, 1H), 4.96 (m, 1H), 7.26 (d, 2H), 8.41 (broad s, 3H).

A stirred suspension of 37 (0.38 g) in a solution of Et₃N (0.31 mL) and THF (10 mL), under nitrogen, was treated with ethyl dithioacetate (0.13 mL, about 7 drops) and kept at ambient temperature for 7 d; the reaction was followed by TLC (8% MeOH-0.5% NH₄OH-CHCl₃). Additional ethyl dithioacetate (2 drops) was added after 24 h; after 30 h CH₂Cl₂ (10 mL,) and ethyl dithioacetate (3 drops) were added; after 48 h additional triethylamine (0.3 mL) was added. The mixture was concentrated in vacuo and the residue was mixed with ice and saturated NaHCO₃ an extracted with CH₂Cl₂. The extract was washed with water and brine, dried (MgSO₄) and concentrated. The residue was chromatographed on silica gel with 2.5% MeOH-CH₂Cl₂ and the product was crystallized from MeOH to give 0.182 g of 38: mp 110-111° C. (dec); MS(ES) m/z 429 (M+H⁺), 451 (M+Na⁺); HRMS (FAB) calcd for C₁₈H₂₃F₂N₄O₄S (M+H⁺) 429.1408, found 429.1415; IR (DRIFT) 1760, 1652, 1639 cm⁻¹; [α²⁴ _(D) 8° (MeOH).

EXAMPLE 30 (S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea (44).

A solution of 26 (0.190 g, 0.685 mmol) in CH₂Cl₂ (20 mL) was added, dropwise during 20 min, under nitrogen, to an ice cold, stirred solution of 1,10-thiocarbonyldi-2(1H)-pyridone (0.193 g, 0.831 mmol) in CH₂Cl₂ (7 mL). The mixture was kept in the ice bath for 20 min and at ambient temperature for 2 h, diluted with CH₂Cl₂, washed with water and brine, dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel with 10-15% CH₃CN-CH₂Cl₂ gave 0.11 g of 79 which was used in the next reaction without further purification: MS(ES) m/z 320 (M+H⁺), 342 (M+Na⁺).

A stirred, ice cold solution of 79 (0.10 g, 0.31 mmol) in THF (15 mL) was treated with excess anhydrous ammonia and kept in the ice bath for 90 min. It was then evaporated under a stream of nitrogen to a volume of about 5 mL to give a solid which was collected by filtration and washed with cold THF to give 0.105 g of 44: mp 214-215° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 3.82 (m, 3H), 4.18 (t, 1H), 4.89 (broad s, 1H), 7.20 (broad s, 2H), 7.50 (d, 1H), 7.79 (m, 2H), 7.93 (t, 1H), 8.26 (s, 1H), 8.97 (s, 1H); MS(ES) m /z 337 (M+H⁺), 359 (M+Na⁺). Anal. calcd for C₁₃H₁₃FN₆O₂S: C, 46.42; H, 3.90; N, 24.99. Found: C, 46.22; H, 3.98; N, 24.55.

EXAMPLE 31 (S)-N[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]thiourea (45).

An ice cold, stirred solution of 1,10-thiocarbonyl-2(1H)-dipyridone (0.123 g, 0.530 mmol) in CH₂Cl₂ (5 mL), under nitrogen, was treated with a suspension of 29 (0.17 g, 0.4 mmol) in CH₂Cl₂ (20 mL) and then during 10 min with a solution of triethylamine (0.111 mL, 0.8 mmol) in CH₂Cl₂ (10 mL). It was kept in the ice bath for 30 min, at ambient temperature for 2 h and at <0° C. for 18 h. It was then diluted with CH₂Cl₂, washed with water and brine, dried (MgSO₄) and concentrated. The residue (80) was used without further purification in the next reaction. A sample of 80 that was purified by flash chromatography on silica gel with 10-20% acetonitrile-CH₂Cl₂ had: ¹H NMR (300 MHz, CDCl₃) d 1.60 (broad s), 3.07 (m, 4H), 3.45 (m, 2H), 3.85 (m, 4H), 3.97 (d,d, 1H), 4.16 (t, 1H), 4.21 (s, 2H), 4.82 (m, 1H), 6.95 (t, 1H), 7.13 (d,d, 1H), 7.47 (d,d, 1H); MS m/z 395 (M+H⁺); 417 (M+Na⁺).

Excess anhydrous ammonia was bubbled into a stirred, ice cold solution of 80 (crude product from the previous reaction) in THF (25 mL) and the mixture was kept in the ice bath for 90 min and concentrated under a stream of nitrogen. The residue was chromatographed on silica gel with 5% MeOH-0.4% NH₄OH-CHCl₃ and the product was crystallized from acetonitrile to give 0.0544 g of 45: mp 209-210° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 294 (broad s, 4H), 3.47 (broad s, 2H), 3.60 (broad S, 2H), 3.78 (broad s, 3H), 4.07 (t, 1H), 4.10 (d, J=5.5 Hz, 2H), 4.63 (t, J=5.5 Hz, 1H), 4.81 (broad s, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.15 (broad s, 2H), 7.49 (d,d, 1H), 7.91 (t, 1H); IR (mull) 3443, 3403, 3321, 3202, 3081, 1753, 1655, 1648 cm⁻¹; HRMS (FAB) calcd for C₁₇H₂₃FN₅O₄S (M+H⁺) 412.1454, found 412.1447. Anal. calcd for C₁₇H₂₂FN₅O₄S: C, 49.63; H, 5.39; N, 17.02. Found: C, 49.63; H, 5.48; N, 16.99.

EXAMPLE 32 (S)-N-[[3-[1 -(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thiourea (46).

An ice cold, stirred solution of 1,10-thiocarbonyldi-2(1H)-pyridone (0.096 g, 0.41 mmol) in CH₂Cl₂ (5 mL) was treated with a suspension of 27 (0.10 g, 0.34 mmol) in CH₂Cl₂ (15 ml) and then with 0.05 mL (0.36 mmol) of triethylamine. It was kept in the ice bath for 30 min and at ambient temperature for 2 h, diluted with CH₂Cl₂, washed with water and brine, dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel with 20-40% CH₃CN-CH₂Cl₂ gave 0.04 g of 81.

Excess anhydrous ammonia was bubbled into an ice cold solution of 81 (0.04 g) in THF (30 mL) and the mixture was kept in the ice bath for 80 min and concentrated under a stream of nitrogen. The residue was crystallized from CH₃CN to give 0.0151 g of 46: mp 214-215° C. (dec); MS (FAB) m/z 351 (M+H⁺), 350 (M⁺), 319, 304, 147; HRMS (FAB) calcd for C₁₅H₁₉N₄O₄S (M+H⁺) 351.1127, found 351.1130; IR (DRIFT) 3329, 3296, 3196, 1746, 1655, 1626 cm⁻¹.

EXAMPLE 33 (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiomorpholine S-oxide (47).

A suspension of 33 (0.30 g, 0.92 mmol) in CH₂Cl₂ (7 mL) was added, during 20 min, to an ice cold, stirred mixture of 1,1-thiocarbonyldi-2(1H)-pyridone (0.258 g, 1.11 mmol) and CH2Cl₂ (20 mL). The mixture was kept in the ice bath for 20 min and at ambient temperature for 2 h, mixed with CH₂Cl₂ (50 mL), washed with water and brine, dried (MgSO₄) and concentrated. Chromatography of the product on silica gel with 20-50% CH₃CN-CH₂Cl₂ gave 0.27 g of 82 which was used in the next reaction: MS(ES) m/z 370 (M+H⁺), 392 (M+Na⁺).

A stirred, ice cold solution of 82 (0.27g, 0.73 mmol) in THF (15 mL), under nitrogen, was treated with excess anhydrous ammonia, kept in the ice bath for 1 h and concentrated; crystallization of the residue from MeOH gave 0.175 g of 47; mp 212-213° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.83 (m, 2H), 3.01 (m, 2H), 3.17 (m, 2H), 3.50 (t, 2H), 3.78 (broad s, 3H), 4.08 (t, 1H), 4.80 (broad s, 1H), 7.17 (m, 2H), 7.17 (broad s, 2H), 7.50 (d, 1H), 7.90 (t, 1H); MS(ES) m/z 409 (M+Na⁺); IR (mull) 3335, 3284, 3211, 3175, 3097, 1750, 1630 cm⁻¹. Anal. calcd for C₁₅H₁₉FN₄O₃S₂: C, 46.62; H, 4.95; N, 14.50. Found: C, 46.50; H, 4.95; N, 14.40.

EXAMPLE 34 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl-S-methyldithiocarbamate (48).

An ice cold, stirred mixture of 39 (0.59 g, 0.0020 mol), EtOH (1.5 mL), water (2 drops) and triethylamine (0.613 mL, 0.00440 mol), under nitrogen, was treated with carbon disulfide (0.066 mL, 0.0011 mol) and kept in the ice bath for 2 h and at ambient temperature for 18 h. (A solution was obtained after the addition of carbon disulfide; a white precipitate began to form soon after the mixture was warmed to ambient temperature.) The thick suspension was treated, dropwise during 2 min, with a solution of methyl iodide (0.137 mL, 0.00220 mol) in EtOH (2 mL) and the mixture was kept at ambient temperature for 1.5 h and concentrated in vacuo. A solution of the residue in EtOAc was washed with saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated. The residue was chromatographed on silica gel with 1.8% MeOH-CH₂Cl₂ and the product was crystallized from EtOAc to give 0.197 g of 48: mp 154-155° C.; IR (mull) 3354, 3346, 1726 cm⁻¹. Anal. calcd for C₁₆H₂₀FN₃O₃S₂: C, 49.85; H, 5.23; N, 10.90. Found: C, 49.73; H, 5.25; N, 10.82.

EXAMPLE 35 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oazolidinyl]methyl-O-methylthiocarbamate (50).

A stirred mixture of 48 (0.200 g, 0.518 mmol), sodium methoxide (0.003 g, 0.06 mmol) and MeOH (5 mL), under nitrogen, was refluxed for 4 h and kept at ambient temperature for 18 h. It was found that the starting material and product had similar mobilities on TLC. The reaction was therefore followed by MS(ES). Starting material was still present. The mixture was refluxed for 3 h, additional sodium methoxide (0.005 g) was added and reflux was continued for 2 h. It was kept at ambient temperature for 18 h, refluxed for 1 h, kept at ambient temperature 1.5 h and concentrated in vacuo. The residue was mixed with ice, the pH was adjusted to 9-10 with 1M KHS04 and saturated NaHCO₃ and the mixture was extracted with CH₂Cl₂. The extract was washed with water and brine, dried (MgSO₄) and concentrated. The residue was chromatographed on silica gel with 5% acetone-CH₂Cl₂ and the product was crystallized from EtOAc-hexane to give 0.107 g of 50: mp 128-129° C.; MS(ES) m/z 370 (M+H⁺), 392 (M+Na⁺); IR (DRIFT) 3282, 3251, 1753, 1735 cm⁻¹; ¹H NMR 1300 MHz, (CD₃)₂SO] d 2.94 (m, 4H), 3.47, 374 (m,m, 7H), 3.86, 3.91 (s,s, 3H), 4.10 (m, 1H), 4.73, 4.86 (m,m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d, 1H), 9.41, 9.50 (s,s, 1H). Anal. calcd for C₁₆H₂₀FN₃O₄S: C, 52.02; H, 5.46; N, 11.38. Found: C, 51.97; H, 5.49; N, 11.35.

When in the procedure of Example 35 an appropriate amount of sodium ethoxide was substituted for sodium methoxide, the compound of Example 36 below in Table A was obtained.

When in the procedure of Example 1 an appropriate amount of (S)-N-[[3-[3-fluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isopropylcarboxamide, (S)-N-[[3-[3-fluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropylcarboxanide, or (S)-N-[[3-[3,5-difluoro-4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide was substituted for (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]acetamide (Compound 1l) and the general procedures of Example 1 was followed, the compounds of Examples 37, 38 and 39 respectively as set forth below in Table A were obtained. The isopropylcarboxamide and the cyclopropylcarboxamide are obtained by following the procedure in Example 5 of U.S. Pat. No. 5,688,792 only substituting isobutyric anhydride and cyclopropane carbonyl chloride respectively for acetic anhydride in step 7. The acetamide is obtained as described in U.S. Pat. No. 5,688,792 at Example 4.

When in the procedure of Example 5, step B, an excess amount of dimethylamine in THF is substituted for anhydrous ammonia, the compound of Example 40 set forth below in Table A is obtained.

TABLE A

Example No. Compound R, R′ 36 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)- R = H, R′ = OC₂H₅ phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate; mp 120° C., MS(ES) m/z 384 (M + H⁺). Anal. calc for C₁₇H₂₂FN₃O₄S: C, 53.25; H, 5.78; N, 10.96. Found: C, 53.23; H, 5.82; N, 10.92. 37 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)- R = H, R′ = CH(CH₃)₂ phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide; mp 152-153° C. (dec.); Anal. calcd for C₁₈H₂₄FN₃O₃S: C, 56.67; H, 6.34; N, 11.02. Found: C, 56.58; H, 6.41; N, 10.81 38 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropane-carbothioamide; mp 155-156 ° C.; Anal. calcd for C₁₈H₂₂FN₃O₃S: C, 56.98; H, 5.84; N, 11.07. Found C, 56.98; H, 5.85; N, 10.97

39 (S)-N-[[3-[3,5-Difluoro-4-(4-morpholinyl)- R = F, R′ = CH₃ phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide 40 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)- R = H, R′ = N(CH₃)₂ phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′- dimethylthiourea PREPARATION Z Methyl Dithiopropionate

A stirred mixture of magnesium turnings (12.6 g, 0.520 g atom) and THF (100 mL) under nitrogen is treated with a crystal of iodine and about 5% of a solution of bromoethane (30.0 mL, 0.40 mol) in THF (200 mL). When the reaction starts, the remainder of the bromoethane solution is added, dropwise at a rate sufficient to maintain a gentle reflux. After the addition, stirring is continued for 1 hour; the resulting solution is cooled to −20° C. and treated, during 10 minutes with carbon disulfide (24.0 mL, 0.40 mol). The mixture is warmed to 15° C., treated with methyl iodide (28.0 mL, 0.45 mol) and kept at 60° C. for 1 hour. It is then cooled in an ice bath, treated with ice and extracted with Et₂O. The extract is washed with brine, dried (MgSO₄) and concentrated. Distillation of the residue gives 34.0 g of the titled product, bp 48-52° C. (12 mmHg).

The following methyl dithio compounds were obtained when the appropriate alkyl magnesium bromide was substituted for ethyl magnesium bromide in the above procedure:

TABLE B

Rs = (b) (CH₃)₂CH— (h)

(c)

(i)

(d) CH₃CH₂CH₂— (j)

(e)

(k)

(f)

(l)

(g) (CH₃)₃C—CH₂— (m)

When following the general procedure of Example 27, step 4, an appropriate amount of the amine listed below is reacted with the dithio compound listed below the respective compounds, Examples 41 to 61 of Table C are obtained.

When following the general procedure of Example 25, step 6, an appropriate amount of the amine listed below is reacted with the dithio compound listed below, the respective compounds, Examples 62 to 67, of Table C are obtained.

TABLE C Example Dithio Compound No. Compound Amine (from Preparation Z) 41 (S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S-oxide; mp 196-197° C.; Anal. calcd for C₁₇H₂₂FN₃O₃S₂: C, 51.11; H, 5.55; N, 10.52; S, 16.05. Found: C, 50.99; H, 5.60; N, 10.55; S, 15.75

Z (a) 42 S)-N-[[3-[3-Fluoro-4-(4- Same as above Z (b0 thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S-oxide; mp 195-196° C.; Anal. calcd for C₁₈H₂₄FN₃O₃S₂: C, 52.28; H, 5.85; N, 10.16; S, 15.51. Found: C, 52.24; H, 5.97; N, 10.16; S, 15.28 43 (S)-N-[[3-[3-Fluoro-4- Same as above Z (c) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholine S-oxide; mp 109-110° C.; Anal. calcd for C₁₈H₂₂FN₃O₃S₂; C, 52.54; H, 5.39; N, 10.21; S, 15.58; Found: C, 52.48; H, 5.51; N, 10.28; S, 12.59 44 (S)-N-[[3-[3-Fluoro-4- Same as above Z (d) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide, thiomorpholine S-oxide 45 (S)-N-[[3-[3-Fluoro-4- Same as above Z (e) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide, thiomorpholine S-oxide 46 (S)-N-[[3-[3-Fluoro-4- Same as above Z (f) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide, thiomorpholine S-oxide 47 (S)-N-[[3-[3-Fluoro-4- Same as above Z (g) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide, thiomorpholine S-oxide 48 (S)-N-[[3-[3-Fluoro-4- Same as above Z (h) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothio- amide, thiomorpholine S-oxide 49 (S)-N-[[3-[3-Fluoro-4- Same as above Z (i) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- cyclopentanecarbothio- amide, thiomorpholine S-oxide 50 (S)-N-[[3-[3-Fluoro-4- Same as above Z (j) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothio- amide, thiomorpholine S-oxide 51 (S)-N-[[3-[3-Fluoro-4- Same as above Z (k) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide, thiomorpholine S-oxide 52 (S)-N-[[3-[3-Fluoro-4- Same as above Z (l) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide, thiomorpholine S-oxide 53 (S)-N-[[3-[3-Fluoro-4- Same as above Z (m) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylenethanethio- amide, thiomorpholine S-oxide 54 (S)-N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide, thiomorpholine S-oxide

Ethyl dithioacetate 55 (S)-N-[[3-[3,5-Difluoro- Same as above Z (a) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S-oxide 56 (S)-N-[[3-[3,5-Difluoro- Same as above Z (b) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S-oxide 57 (S)-N-[[3-[3,5-Difluoro- Same as above Z (c) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholine S-oxide 58 (S)-N-[[3-[4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide, thiomorpholine S-oxide

Ethyl dithioacetate 59 (S)-N-[[3-[4-(4- Same as above Z (a) thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S-oxide 60 (S)-N-[[3-[4-(4- Same as above Z (b) thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S-oxide 61 (S)-N-[[3-[4-(4- Same as above Z (c) thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholine S-oxide 62 (S)-N-[[3-[3,5-Difluoro- 4-(4-hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide

Z (a) 63 (S)-N-[[3-[3,5-Difluoro- Same as above Z (b) 4-(4-hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide 64 (S)-N-[[3-[3,5-Difluoro- Same as above Z (c) 4-(4-hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]cyclopropane- thioamide 65 (S)-N-[[3-[3-[4- (hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide

Z (a) 66 (S)-N-[[3-[3-[4- Same as above Z (b) (hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]2-methyl- propanethioamide 67 (S)-N-[[3-[3-[4- Same as above Z (c) (hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide

When following the procedure of Example 28, step 3, an appropriate amount of the amine listed below is reacted with the dithio compound listed below, the respective compounds, Examples 68 to 78 of Table D are obtained.

TABLE D Example Dithio Compound No. Compound Amine (see Preparation Z) 68 (S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S,S- dioxide

Z (a) 69 (S)-N-[[3-[3-Fluoro-4- Same as above Z (b) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S,S-dioxide 70 (S)-N-[[3-[3-Fluoro-4- Same as above Z (c) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholine S,S-dioxide 71 (S)-N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]- methyl]thioacetamide, thiomorpholine S,S- dioxide

Ethyl dithioacetate 72 (S)-N-[[3-[3,5-Difluoro- Same as above Z (a) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S,S- dioxide 73 (S)-N-[[3-[3,5-Difluoro- Same as above Z (b) 4-(4-thiomorpholinyl)- phenyl]2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S,S-dioxide 74 (S)-N-[[3-[2,5-Difluoro- Same as above Z (c) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cylcopropanecarbothio- amide, thiomorpholine S,S-dioxide 75 (S)-N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]thioacetamide, thiomorpholine S,S- dioxide

Ethyl dithioacetate 76 (S)-N-[[3-[4-(4-thio- Same as above Z (a) morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide, thiomorpholine S,S-dioxide 77 (S)-N-[[3-[4-(4-thio- Same as above Z (b) morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide, thiomorpholine S,S- dioxide 78 (S)-N-[[3-[4-(4-thio- Same as above Z (c) morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide, thiomorpholine S,S- dioxide

When following the procedure of Example 26, an appropriate amount of the amine listed below is reacted with the dithio compound listed below the respective compounds, Examples 79 to 99 of Table E are obtained.

TABLE E Example Dithio Compound No. Compound Amine (See Preparation Z) 79 (S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide

Z (a) 80 (S)-N-[[3-[3-Fluoro-4- Same as above Z(b) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 81 (S)-N-[[3-[3-Fluoro-4- Same as above Z (c) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide 82 (S)-N-[[3-[3-Fluoro-4- Same as above Z (d) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide 83 (S)-N-[[3-[3-Fluoro-4- Same as above Z (e) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide 84 (S)-N-[[3-[3-Fluoro-4- Same as above Z (f) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide 85 (S)-N-[[3-[3-Fluoro-4- Same as above Z (g) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide 86 (S)-N-[[3-[3-Fluoro-4- Same as above Z (h) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothio- amide 87 (S)-N-[[3-[3-Fluoro-4- Same as above Z (i) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothio- amide 88 (S)-N-[[3-[3-Fluoro-4- Same as above Z (j) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothio- amide 89 (S)-N-[[3-[3-Fluoro-4- Same as above Z (k) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide 90 (S)-N-[[3-[3-Fluoro-4- Same as above Z (l) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide 91 (S)-N-[[3-[3-Fluoro-4- Same as above Z (m) (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide 92 (S)-N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide

Ethyl dithioacetate 93 (S)-N-[[3-[3,5-Difluoro- Same as above Z (a) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 94 (S)-N-[[3-[3,5-Difluoro- Same as above Z (b) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 95 (S)-N-[[3-[3,5-Difluoro- Same as above Z (c) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide 96 (S)-N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]thioacetamide

Ethyl dithioacetate 97 (S)-N-[[3-[4-(4-thio- Same as above Z (a) morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide 98 (S)-N-[[3-[4-(4-thio- Same as above Z (b) morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide 99 (S)-N-[[3-[4-(4-thio- Same as above Z (c) morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide

The amine utilized in Examples 41 to 53 is prepared as described in Example 27, step 3. The amine utilized in Examples 54 to 57 is prepared by the procedure of Example 27, steps 1 to 3 by substituting the appropriate (S)-N-[[3-[3,5-difluoro-4-(4-thio-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanol for compound 62 in step 1 of Example 27.

The amine utilized in Examples 58 to 61 is prepared by the procedure of Example 27, steps 1 to 3 by substituting the appropriate (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo5-oxazolidinyl]methanol for compound 62 in Example 27, step 1. The appropriate oxazolidinyl methanol compound is obtained by following the procedure of Example 1 in U.S. Pat. No. 5,688,792, steps 1 through 3, only substituting 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in step 1 thereof.

The amine utilized in Examples 62 to 64 is prepared as compound 37 in Example 29 from the amide, 65, which is prepared as described in Example 32 of U.S. Pat. No. 5,700,799. The amine utilized in Examples 65 to 67 is prepared by the general procedure of Example 29 from the following amide, the preparation of which is described in Example 3 of U.S. Pat. No. 5,700,799:

The amine utilized in Examples 68 to 70 is prepared as described in step 2 of Example 28 above.

The amine utilized in Examples 71 to 74 is prepared as described in Example 28 by substituting (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanol for compound 62 in step 1 and following the procedure of steps 1 and 2. The appropriate oxazolidinyl methanol compound is prepared by following the general procedure of Example 4 of U.S. Pat. No. 5,688,792, steps 1 through 4, only substituting thiomorpholine for morpholine in step 1 thereof.

The amine utilized in Examples 75 to 78 is prepared as described in Example 28, step 1, above by substituting (S)-N-[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanol for compound 62 in step 1. The appropriate oxazolidinyl methanol is obtained by following the procedure of Example 1 in U.S. Pat. No. 5,688,792, steps 1 through 3, only substituting 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in step 1 thereof.

The amine utilized in Examples 79 to 91 is prepared as described in Example 1, step 4, of U.S. Pat. No. 5,688,792. The amine utilized in Examples 92 to 95 is prepared as described in Example 4 of U.S. Pat. No. 5,688,792 only substituting thiomorpholine for morpholine in step 1 thereof. The amine utilized in Examples 96 to 99 is prepared by the procedure of Example 1 of U.S. Pat. No. 5,688,792, only substituting 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in step 1 thereof.

EXAMPLE 100 (S)-N-[[3-[3-Fluoro4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S-oxide

A solution of 201 mg (0.554 mmol) of (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate, thiomorpholine s-oxide compound 82 from Example 33, step 1, in methanol (10 mL) is refluxed, under nitrogen for 18 hours and cooled. The solid is collected by filtration to give 0.138 g of the titled product. m.p. 208-209° C.; Anal. calcd for C₁₆H₂₀FN₃O₄S₂: C, 47.87; H, 5.02; N, 10.47. Found: C, 47.81; H, 5.04: N, 10.49.

When in the procedure of Example 100 the thioisocyanate listed below is substituted for compound 82 the products listed below as Examples 101 to 109 are obtained.

TABLE F Isothiocyanate

Example Rc Ra Rb No. Compound OS F F 101 (S)-N-[[3-[3,5-Difluoro-4-(4- thiomorpholinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthio- carbamate, thiomorpholine-S-oxide OS H H 102 (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2- oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate, thiomorpholine S-oxide O₂S H F 103 (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- methylthiocarbamate, thiomorpholine S,S- dioxide O₂S F F 104 (S)-N-[[3-[3,5-Difluoro-4-(4- thiomorpholinyl)phenyl]-2-oco-5- oxazolidinyl]methyl]-O-methylthio- carbamate, thiomorpholine S,S-dioxide O₂S H H 105 (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2- oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate, thiomorpholine S,S-oxide S H F 106 (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- methylthiocarbamate S F F 107 (S)-N-[[3-[3,5-Difluoro-4-(4-thiomorph- olinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate S H H 108 (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2- oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate

H H 109 (S)-N-[[3-[3-Fluoro-4-(4-hydroxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate

When in the procedure of Example 100 an appropriate amount of ethanol and isopropyl alcohol were substituted for methanol, the following respective compounds were obtained:

EXAMPLE 110

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate, thiomorpholine S-oxide. m.p. 198-199° C.; Anal. calcd for C₁₇H₂₂FN₃O₄S₂: C, 49.14; H, 5.34; N, 10.11. Found: C, 49.06; H, 5.27; N, 10.10.

EXAMPLE 111

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiomorpholine S-oxider m.p. 180-181° C.; Anal. calcd for C₁₈H₂₄FN₃O₄S₂: C, 50.33; H, 5.63; N, 9.78. Found: C, 50.29; H, 5.69; N, 9.82.

When in the procedure of Example 100 an appropriate amount of (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]isothiocyanate is substituted for compound 82 and ethanol or isopropyl alcohol is substituted for methanol, the following respective products are obtained:

EXAMPLE 112

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate;

EXAMPLE 113

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-iso-propylthiocarbamate;

EXAMPLE 114

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N-methylthiourea, thiomorpholine S-oxide.

A stirred suspension of 240 mg (0.650 mmol) of compound 82 from Example 33, step 1 in THF (5 mL) at 0° C. is treated with a 2M solution of methylamine in THF (0.42 mL, 0.845 mmol) and kept at ambient temperature for 18 hours. The solid is collected by filtration to give 0.221 g of the titled product.

Following the procedure of Example 114, only substituting an appropriate amount of dimethylamine and azetidine for methylamine, the following compounds are obtained:

EXAMPLE 115

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea, thiomorpholine S-oxide; Anal. Calcd for C₁₇H₂₃FN₄O₃S₂, C, 49.26; H, 5.59; N, 13.52. Found C, 49.11; H, 5.57; N, 13.40; mp 180-182° C.

EXAMPLE 116

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiomorpholine S-oxide; Anal. Calcd for C₁₈H₂₃FN₄O₃S₂, C, 50.69; H, 5.43; N, 13.14. Found: C, 50.79; H, 5.45; N, 12.82; mp 213-214° C.

When in the procedure of Example 114 an appropriate amount of (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinylophenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate is substituted for compound 82, the following compound is obtained:

EXAMPLE 117

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methyl-N′-methylthiourea.

When in the procedure of Example 117 an appropriate amount of dimethylamine and azetidine are substituted for methylamine, the following respective products are obtained:

EXAMPLE 118

(S)-N-[[3-[3-Fluoro4-(4thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea;

EXAMPLE 119

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide.

When in the procedure of Example 33 an appropriate amount of compound 31 from Example 26 is substituted for compound 33 and the general procedure of steps 1 and 2 of Example 33 are followed, the following compound is obtained.

EXAMPLE 120

(S)-N-[[3-[3-Fluoro4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea.

EXAMPLE 121

(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl-2-oxo-5-oxazolidinyl]methyl]propanethioanmide

A stirred mixture of 200 mg (0.514 mmol) of 29 methyl dithiopropionate (247 mg, 2.06 mmol), triethylamine (0.58 mL, 4.11 mmol), THF (5.4 mL) and methylene chloride (5.4 mL) is kept, under nitrogen, for 3 days, diluted with water and extracted with methylene chloride. The extracts are dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel and crystallization of the product from methanol gives 0.132 g of the titled product. m.p. 190-191° C.; Anal. calcd for C₁₉H₂₅FN₄O₄S: C, 53.76; H, 5.94; N, 13.20; S, 7.55. Found: C, 53.66; H, 5.94; N, 13.20; S, 7.37.

Following the procedure of Example 121 only substituting dithio compounds Z (b) to Z (m) from Preparation Z above for methyl dithiopropionate, the following compounds are obtained.

TABLE G

Example No. Compound 122 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- R = CH(CH₃)₂ acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropane- thioamide; Anal. calcd for C₂₀H₂₇FN₄O₄S: C, 54.78; H, 6.21; N, 12.78; S, 7.31. Found: C, 54.67; H, 6.34; N, 12.41; S, 7.15 123 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopropane- carbothioamide; mp 179-181° C.; Anal. calcd for C₂₀H₂₅FN₄O₄S: C, 55.03; H 5.77; N, 12.84; S, 7.34. Found: C, 55.15; H, 5.72; N, 12.76; S, 7.09

124 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- R = CH₂—CH₂—CH₃ acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]butanethioamide 125 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3-methylbutane- thioamide

126 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylbutane- thioamide

127 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- R = CH₂—C(CH₃)₃ acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3,3-dimethyl- butanethioamide 128 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclobutane- carbothioamide

129 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopentane- carbothioamide

130 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclohexane- carbothioamide

131 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclopropyl- ethanethioamide

132 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclobutyl- ethanethioamide

133 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxy- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclopentyl- ethanethioamide

When in the procedure of Example 100 an appropriate amount of compound 80 from Example 31 is substituted for compound 82, and ethanol or isopropyl alcohol is substituted for methanol, the following respective compounds are obtained:

EXAMPLE 134

(S)-N-[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate;

EXAMPLE 135

((S)-N-[[3-[3-Fluoro4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-iso-propylthiocarbamate;

EXAMPLE 136

(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea.

When in the procedure of Example 114 an appropriate amount of compound 80 from Example 31 is substituted for compound 82, the title compound is obtained.

Following the procedure of Example 114 only substituting an appropriate amount of compound 80 from Example 31 for compound 82 and substituting an appropriate amount of dimethylamine and azetidine for methylamine, the following compounds, Examples 137 and 138, are obtained:

EXAMPLE 137

(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea;

EXAMPLE 138

(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide.

EXAMPLE 139 (S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate.

Part A:

Following the procedure of Example 33, step 1, only substituting an appropriate amount of compound 37 from Example 29, step 5, for compound 33, (S)-N-[[3,5-[3-difluoro4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]isothiocyanate is obtained.

Part B:

Upon substitution of an appropriate amount of (S)-N-[[3-[3,5-difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate for compound 82 in the general procedure of Example 100, the title compound is obtained.

EXAMPLE 140 (S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate

Part A:

Following the procedure of Example 33, step 1, only substituting an appropriate amount of (S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine for compound 33, (S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate is obtained.

Part B:

Upon substituting an appropriate amount of (S)-N-[[3-[4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate for compound 82 in the general procedure of Example 100, the title compound is obtained.

EXAMPLE 141 (S)-N-[[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidiny]methyl]thioacetamide

An ice cold, stirred solution of 30.4 g (70.8 mmol) of starting material 58 from Example 25, step 1), and triethylamine (15.4 mL, 110 mmol) in methylene chloride (2570 mL) is treated with m-nitrobenzenesulfonyl chloride (18.8 g, 84.9 mmol) and kept, under nitrogen, at ambient temperature (24° C.) for 24 hours. Additional m-nitrobenzenesulfonyl chloride (1.88 g) and triethylamine (1.54 mL) are added and the mixture is kept for one additional day at ambient temperature, washed with water, saturated sodium bicarbonate and brine, dried (Na₂SO₄) and concentrated to give an oily product, 85. The alcohol, 58 is prepared according to the procedures of Brickner (J. Med. Chem. 1996, 39 673-679), see compound 5a therein.

A stirred mixture of 85, acetonitrile (1270 mL), isopropanol (1270 mL) and ammonium hydroxide (1270 mL) is kept at ambient temperature for 3 days and concentrated in vacuo. Chromatography of the residue on silica gel with 0.5% NH₄OH-1% MeOH—CH₂Cl₂ gives 22.4 g of the amine, 86.

An ice cold, stirred solution of the amine 86 in THF (650 mL) is treated, during 20 minutes with a solution of di-tert-butyl dicarbonate (12.0 g, 55.2 mmol) in THF (90 mL). The mixture is kept at ambient temperature for 18 hours and concentrated in vacuo. The residue, dissolved in methylene chloride, is washed with dilute sodium bicarbonate, dried (MgSO₄) and concentrated. Crystallization of the residue from methanol-ethyl acetate gives 20.0 g of the Boc protected amine. Additional product (4.1 g) is obtained by chromatographing the mother liquors on silica gel with 1-2% methanol-methylene chloride.

A solution of the protected amine, 87, (5.00 g, 9.46 mmol) in ethanol (150 mL) is treated with 10% palladium-on-carbon catalyst (1.0 g) and hydrogenated at an initial pressure of 30 psi for 3 hours. The catalyst is removed by filtration through Celite and the filtrate was concentrated to give 3.66 g of compound 88.

A stirred solution of compound 88 (1.10 g, 2.79 mmol) in pyridine (10 mL) is treated with acetic anhydride (289 μL, 3.07 mmol), kept at ambient temperature for 2 hours and concentrated in vacuo. A solution of the residue in methylene chloride is washed with dilute hydrochloric acid, dried (MgSO₄) and concentrated to give 1.23 g of compound 89: MS m/z 436 (M⁺).

An ice cold, stirred 4N solution of HCl in dioxane (10 mL) is treated with compound 89 (1.10 g, 2.52 mmol). The mixture is kept in the ice bath for 30 minutes and at ambient temperature for 1 hour. It was then mixed with methylene chloride and concentrated. The residue is triturated with methylene chloride to give 1.03 g of the amine hydrochloride.

A stirred mixture of compound P-90 (250 mg), triethylamine (0.75 mL, 5.36 mmol), ethyl dithioacetate (307 μL, 2.68 mmol), methylene chloride (7.4 mL) and THF (7.4 mL) is kept at ambient temperature for 1 day, concentrated and chromatographed on silica gel with mixtures of methanol-methylene chloride containing 1-2% methanol. Crystallization of the product from ethyl acetate-heptane gives 0.160 g of the titled product: Anal. calcd for C₁₈H₂₃FN₄O₃S: C, 54.81; H, 5.88; N, 14.20; S, 8.13. Found: C, 54.92; H, 5.95; N, 14.08; S, 7.94; mp 158° C.

When in the general procedure of Example 141 an appropriate amount of

is substituted for compound 58 and the procedure of steps 1 through 6 are followed, the respective amine compounds P-91 and P-92 listed below are obtained:

The alcohols above designated as x and y are prepared according to the procedures of Brickner (J. Med. Chem., 1996, 39, 673-679), by substituting an appropriate amount of 2,6-difluoro-4-nitrobenzene (trifluoromethane) sulfonate and 4-fluoronitrobenzene respectively for 3,4-difluoronitrobenzene in the preparation of 2a therein.

When in the procedure of Example 141 an appropriate amount of x or y is substituted for compound 58 and the procedures of steps 1 through 4 are followed, the following Boc protected compounds listed below are obtained.

When in the procedure of Example 141, step 5, an appropriate amount of compound 88, compound x-b or compound y-b is treated with the reagent listed below and the general procedures of step 5 and step 6 are followed, the amines listed below as Preparation P-93 through P-128 are obtained.

The amine compound set forth below as P-129 is obtained by refluxing for 6 days a solution of compound 88 (1.00 g, 2.54 mmol), sulfamide (305 mg, 3.18 mmol) and 1,2-dimethyoxyethane (6 mL). The solid which precipitates is collected by filtration and chromatographed on silica gel with 5% methanol-methylene chloride. Crystallization of the product from methanol-methylene chloride gives 0.551 g of the sulfamoyl derivative, which is used in step 6 of Example 141 to give P-129. When compounds x-b and y-b are substituted for compound 88 and this general procedure is followed, Preparations P-130 and P-131 respectively set forth below are obtained.

Following the general procedures of steps 5 and 6 of Example 141 only in step 5 substituting chloroacetonitrile or 2-fluoroethyl bromide respectively for acetic anhydride and using potassium carbonate in acetonitrile, and using either compound 88, compound x-b or compound y-b, the respective amines set forth below as Preparations P-132 to P-137 are obtained.

The amine compound set forth below as Preparation P-138 is obtained by combining compound 88 (1.10 g, 2.75 mmol) set forth in step 5 of Example 141 with N-formylbenzotriazole (493 mg, 3.35 mmol) in THF (30 mL) and the mixture is kept at ambient temperature for 18 hours. The mixture is concentrated and the residue in methylene chloride is washed with 1N sodium hydroxide and dilute sodium chloride, dried (MgSO₄), concentrated, and chromatographed on silica gel with mixtures of methanol and methylene chloride containing 1-2% methanol to give 1.09 g of the N-formyl derivative which is utilized in the general procedure of step 6 of Example 141 to give Preparation P-138. When in this foregoing procedure compound x-b or compound y-b is substituted for compound 88, Preparations P-139 and and P-140 as set forth below are obtained.

Boc Preparation Reagent Compound R R″ R′ No. methoxyacetylchloride 88 x-b y-b

H F H F F H P-93 P-94 P-95 cyanoacetyl chloride 88 x-b y-b

H F H F F H P-96 P-97 P-98 acetoxyacetyl chloride 88 x-b y-b

H F H F F H P-99 P-100 P-101 benzyloxyacetyl chloride 88 x-b y-b

H F H F F H P-102 P-103 P-104 methyl chloroformate 88 x-b y-b

H F H F F H P-105 P-106 P-107 methanesulfonyl chloride 88 CH₃SO₂— H F P-108 x-b F F P-109 y-b H H P-110 ethanesulfonyl chloride 88 CH₃CH₂SO₂— H F P-111 x-b F F P-112 y-b H H P-113 chloromethanesulfonyl 88 ClCH₂SO₂— H F P-114 chloride x-b F F P-115 y-b H H P-116 cyanomethanesulfonyl 88 NCCH₂SO₂— H F P-117 chloride x-b F F P-118 y-b H H P-119 N-methylsulfamoyl 88 CH₃NHSO₂— H F P-120 chloride x-b F F P-121 y-b H H P-122 N,N-dimethylsulfamoyl 88 (CH₃)₂NSO₂— H F P-123 chloride x-b F F P-124 y-b H H P-125 ethyl chloroformate 88 x-b y-b

H F H F F H P-126 P-127 P-128 sulfamide 88 H₂NSO₂— H F P-129 x-b F F P-130 y-b H H P-131 chloroacetonitrile 88 NCCH₂— H F P-132 x-b F F P-133 y-b H H P-134 2-fluoroethyl bromide 88 FCH₂CH₂— H F P-135 x-b F F P-136 y-b H H P-137 N-formylbenzotriazole 88 x-b y-b

H F H F F H P-138 P-139 P-140

EXAMPLES 142-161

When following the general procedures of Example 141, step 7, an appropriate amount of the amine listed below and the dithio compound from Preparation Z listed below are utilized, the respective products designated as Examples 142 to 400 in Table H are obtained.

TABLE H Example Dithio No. Product Amine Compound 142 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (a) 2-oxo-5-oxazolidinyl]methyl]propanethioamide; mp 161-162° C.; Anal. calcd for C₁₉H₂₅FN₄O₃S: C, 55.87; H, 6.17; N, 13.72; S, 7.85. Found: C, 55.79; H, 6.26; N, 13.60; S, 7.71 143 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (b) 2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide 144 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (c) 2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbo- thioamide; mp 159-160° C.; Anal. calcd for C₂₀H₂₅FN₄O₃S: C, 57.13; H, 5.99; N, 13.32; S, 7.62. Found: C, 57.05; H, 6.01; N, 13.15; S, 7.45. 145 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (d) 2-oxo-5-oxazolidinyl]methyl]butanethioamide 146 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (e) 2-oxo-5-oxazolidinyl]methyl]-3-methylbutane- thioamide 147 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (f) 2-oxo-5-oxazolidinyl]methyl]-2-methylbutane- thioamide 148 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (g) 2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutane- thioamide 149 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (h) 2-oxo-5-oxazolidinyl]methyl]cyclobutanecarbo- thioamide 150 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (i) 2-oxo-5-oxazolidinyl]methyl]cyclopentanecarbo- thioamide 151 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (j) 2-oxo-5-oxazolidinyl]methyl]cyclohexanecarbo- thioamide 152 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (k) 2-oxo-5-oxazolidinyl]methyl]-2-cyclopropylethane- thioamide 153 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (l) 2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethane- thioamide 154 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90 Z (m) 2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethane- thioamide 155 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)- P-91 Ethyl phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 156 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)- P-91 Z (a) phenyl]-2-oxo-5-oxazolidinyl]methyl]propane- thioamide 157 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)- P-91 Z (b) phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl- propanethioamide 158 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)- P-91 Z (c) phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 159 (S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5- P-92 Ethyl oxazolidinyl]methyl]thioacetamide dithio- acetate 160 (S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5- P-92 Z (a) oxazolidinyl]methyl]propanethioamide 161 (S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5- P-92 Z (b) oxazolidinyl]methyl]-2-methylpropanethioamide 162 (S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5- P-92 Z (c) oxazolidinyl]methyl]cyclopropanecarbothioamide 163 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 164 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 165 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 166 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 167 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (d) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide 168 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (e) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide 169 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (f) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylbutanethioamide 170 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (g) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3- dimethylbutanethioamide 171 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (h) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclobutanecarbothioamide 172 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (i) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopentanecarbothioamide 173 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (j) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclohexanecarbothioamide 174 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (k) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopropylethanethioamide 175 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (l) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclobutylethanethioamide 176 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 Z (m) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopentylethanethioamide 177 (S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxyacetyl)-1- P-94 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 178 (S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxyacetyl)-1- P-94 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 179 (S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxyacetyl)-1- P-94 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 180 (S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxyacetyl)-1- P-94 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 181 (S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]- P-95 Ethyl 2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 182 (S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]- P-95 Z (a) 2-oxo-5-oxazolidinyl]methyl]propanethioamide 183 (S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]- P-95 Z (b) 2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide 184 (S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]- P-95 Z (c) 2-oxo-5- oxazolidinyl]methyl]cyclopropanecarbothioamide 185 (S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]- P-96 Ethyl phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 186 (S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]- P-96 Z (a) phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethio- amide 187 (S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]- P-96 Z (b) phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl- propanethioamide 188 (S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]- P-96 Z (c) phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 189 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1- P-97 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- dithio- methyl]thioacetamide acetate 190 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1- P-97 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]propanethioamide 191 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1- P-97 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 192 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1- P-97 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]cyclopropanecarbothioamide 193 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2- P-98 Ethyl oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 194 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2- P-98 Z (a) oxo-5-oxazolidinyl]methyl]propanethioamide 195 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2- P-98 Z (b) oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 196 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2- P-98 Z (c) oxo-5-oxazolidinyl]methyl]cycopropanecarbothio- amide 197 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 198 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 199 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 200 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 201 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (d) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide 202 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (e) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide 203 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (f) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylbutanethioamide 204 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (g) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3- dimethylbutanethioamide 205 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (h) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclobutanecarbothioamide 206 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (i) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopentanecarbothioamide 207 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (j) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclohexanecarbothioamide 208 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (k) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopropylethanethioamide 209 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (l) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methy1]-2- cyclobutylethanethioamide 210 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 Z (m) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopentylethanethioamide 211 (S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1- P-100 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 212 (S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1- P-100 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 213 (S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1- P-100 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 214 (S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1- P-100 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 215 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]- P-101 Ethyl 2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 216 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]- P-101 Z (a) 2-oxo-5-oxazolidinyl]methyl]propanethioamide 217 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]- P-101 Z (b) 2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide 218 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]- P-101 Z (c) 2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbo- thioamide 219 (S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1- P-102 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 220 (S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1- P-102 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 221 (S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1- P-102 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 222 (S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1- P-102 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 223 (S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1- P-103 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 224 (S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1- P-103 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 225 (S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1- P-103 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 226 (S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1- P-103 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 227 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 228 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 229 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 230 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 231 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (d) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide 232 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (e) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide 233 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (f) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylbutanethioamide 234 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (g) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3- dimethylbutanethioamide 235 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (h) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclobutanecarbothioamide 236 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (i) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopentanecarbothioamide 237 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (j) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclohexanecarbothioamide 238 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (k) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopropylethanethioamide 239 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (l) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclobutylethanethioamide 240 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (m) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopentylethanethioamide 241 (S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1- P-106 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 242 (S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1- P-106 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 243 (S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1- P-106 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 244 (S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1- P-106 Z (c) piperazinyl]phenyi]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 245 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 246 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 247 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 248 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 249 (S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1- P-108 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide; mp 197-198° C.; Anal. calcd for acetate C₁₇H₂₃FN₄O₄S₂: C, 47.43; H, 5.39; N, 13.01; S, 14.89. Found: C, 47.25; H, 5.40; N, 12.82; S, 14.56. 250 (S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1- P-108 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide; mp 207-208° C.; Anal. calcd for C₁₈H₂₅FN₄O₄S₂: C, 48.63; H, 5.67; N, 12.60; S, 14.42. Found: C, 48.51; H, 5.59; N, 12.52; S, 14.09. 251 (S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1- P-108 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide; mp 204-206° C.; Anal. calcd for C₁₉H₂₇FN₄O₄S₂: C, 49.76; H, 5.93; N, 12.22; S, 13.98. Found: C, 49.63; H, 5.92; N, 14.14; S, 13.91. 252 (S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1- P-108 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide; Anal. calcd for C₁₉H₂₅FN₄O₄S₂: C, 49.98; H, 5.52; N, 12.27; S, 14.04. Found: C, 49.42; H, 5.50; N, 12.08; S, 13.80. 253 (S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1- P-109 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 254 (S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1- P-109 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 255 (S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1- P-109 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 256 (S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1- P-109 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 257 (S)-N-[[3-[4-[4-(methanesulfonyl)-1- P-110 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 258 (S)-N-[[3-[4-[4-(methanesulfonyl)-1- P-110 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 259 (S)-N-[[3-[4-[4-(methanesulfonyl)-1- P-110 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 260 (S)-N-[[3-[4-[4-(methanesulfonyl)-1- P-110 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 261 (S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1- P-111 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 262 (S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1- P-111 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 263 (S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1- P-111 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 264 (S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1- P-111 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 265 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1- P-112 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 266 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1- P-112 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 267 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1- P-112 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 268 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1- P-112 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 269 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]- P-113 Ethyl 2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 270 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]- P-113 Z (a) 2-oxo-5-oxazolidinyl]methyl]propanethioamide 271 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]- P-113 Z (b) 2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide 272 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]- P-113 Z (c) 2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothio- amide 273 (S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1- P-114 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 274 (S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1- P-114 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 275 (S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1- P-114 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 276 (S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1- P-114 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 277 (S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)- P-115 Ethyl 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 278 (S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)- P-115 Z (a) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 279 (S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)- P-115 Z (b) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 280 (S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)- P-115 Z (c) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 281 (S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1- P-116 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 282 (S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1- P-116 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl] propanethioamide 283 (S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1- P-116 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 284 (S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1- P-116 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 285 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1- P-117 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 286 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1- P-117 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 287 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1- P-117 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 288 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1- P-117 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 289 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)- P-118 Ethyl 1-piperazinyl]pheny1]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 290 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)- P-118 Z (a) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]propanethioamide 291 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)- P-118 Z (b) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 292 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)- P-118 Z (c) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 293 (S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1- P-119 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 294 (S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1- P-119 Z (a) piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 295 (S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1- P-119 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 296 (S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1- P-119 Z (c) piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopropanecarbothioamide 297 (S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1- P-120 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 298 (S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1- P-120 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 299 (S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1- P-120 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 300 (S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1- P-120 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 301 (S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1- P-121 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 302 (S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1- P-121 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 303 (S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1- P-121 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 304 (S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1- P-121 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 305 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1- P-122 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 306 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1- P-122 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 307 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1- P-122 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 308 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1- P-122 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 309 (S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1- P-123 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 310 (S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1- P-123 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 311 (S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1- P-123 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 312 (S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1- P-123 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 313 (S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)- P-124 Ethyl 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 314 (S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)- P-124 Z (a) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 315 (S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)- P-124 Z (b) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 316 (S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)- P-124 Z (c) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 317 (S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1- P-125 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 318 (S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1- P-125 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 319 (S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1- P-125 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 320 (S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1- P-125 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 321 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 322 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 323 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 324 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 325 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (d) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide 326 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (e) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide 327 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (f) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylbutanethioamide 328 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (g) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3- dimethylbutanethioamide 329 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (h) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclobutanecarbothioamide 330 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (i) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopentanecarbothioamide 331 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (j) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclohexanecarbothioamide 332 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (k) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopropylethanethioamide 333 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (l) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclobutylethanethioamide 334 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (m) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopentylethanethioamide 335 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1- P-127 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetmide acetate 336 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1- P-127 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 337 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1- P-127 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 338 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1- P-127 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 339 (S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]- P-128 Ethyl phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 340 (S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]- P-128 Z (a) phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 341 (S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]- P-128 Z (b) phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 342 (S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]- P-128 Z (c) phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 343 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)- P-129 Ethyl phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 344 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)- P-129 Z (a) phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 345 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)- P-129 Z (b) phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 346 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)- P-129 Z (c) phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 347 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (d) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]butanethioamide 348 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (e) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide 349 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (f) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylbutanethioamide 350 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (g) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3- dimethylbutanethioamide 351 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (h) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclobutanecarbothioamide 352 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (i) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopentanecarbothioamide 353 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (j) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclohexanecarbothioamide 354 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (k) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopropylethanethioamide 355 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (l) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclobutylethanethioamide 356 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (m) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopentylethanethioamide 357 (S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1- P-130 Ethyl piperazinyl)phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 358 (S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1- P-130 Z (a) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 359 (S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1- P-130 Z (b) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 360 (S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1- P-130 Z (c) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopropanecarbothioamide 361 (S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo- P-131 Ethyl 5-oxazolidinyl]methyl]thioacetamide dithio- acetate 362 (S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo- P-131 Z (a) 5-oxazolidinyl]methyl]propanethioamide 363 (S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo- P-131 Z (b) 5-oxazolidinyl]methyl]-2-methylpropanethioamide 364 (S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo- P-131 Z (c) 5-oxazolidinyl]methyl]cyclopropanecarbothiomade 365 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1- P-132 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 366 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1- P-132 Z (a) piperazinyl]phenyl]-2-oxo-5- oxazolidiinyl]methyl]propanethioamide 367 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1- P-132 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 368 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1- P-132 Z (c) piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopropanecarbothioamide 369 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)-1- P-133 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]propanethioamide acetate 370 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)-1- P-133 Z (a) piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 371 (S)-N-[[3-[3,5-Difluoro-4-[4 cyanomethyl)-1- P-133 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 372 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)-1- P-133 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 373 (S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-2- P-134 Ethyl oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 374 (S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-2- P-134 Z (a) oxo-5-oxazolidinyl]methyl]propanethioamide 375 (S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-2- P-134 Z (b) oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 376 (S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]- P-134 Z (c) 2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 377 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1- P-135 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 378 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1- P-135 Z (a) piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 379 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1- P-135 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 380 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1- P-135 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 381 (S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1- P-136 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide acetate 382 (S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1- P-136 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 383 (S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1- P-136 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 384 (S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1- P-136 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 385 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]- P-137 Ethyl 2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 386 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]- P-137 Z (a) 2-oxo-5-oxazolidinyl]methyl]propanethioamide 387 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]- P-137 Z (b) 2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 388 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]- P-137 Z (c) 2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 389 (S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]- P-138 Ethyl 2-oxo-5-oxazolidinyl]methyl]thioacetamide; Anal calcd dithio- for C₁₇H₂₁FN₄O₃S: C, 53.67; H, 5.56; N, 14.73; S, acetate 8.43. Found: C, 53.14; H, 5.42; N, 14.25; S, 8.18. 390 (S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]- P-138 Z (a) 2-oxo-5-oxazolidinyl]methyl]propanethioamide; mp 166-167° C.; Anal. calcd for C₁₈H₂₃FN₄O₃S: C, 54.81; H, 5.88; N, 14.20; S, 8.13. Found: C, 54.83; H, 6.00; N, 14.12; S, 7.96. 391 (S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]- P-138 Z (b) 2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide; mp 157-158° C.: Anal. calcd for C₁₉H₂₅FN₄O₃S: C, 55.87, H, 6.17; N, 13.72; S, 7.85. Found: C, 55.67; H, 6.19; N, 13.50; S, 7.70. 392 (S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]- P-138 Z (c) 2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide; mp 178-179° C.; Anal. calcd for C₁₉H₂₃FN₄O₃S: C, 56.14; H, 5.70; N, 13.78; S, 7.89. Found: C, 56.13; H, 5.64; N, 13.64; S. 7.75. 393 (S)-N-[[3-[3,5-Difluoro-4-(4-formyl-1-piperazinyl)- P-139 Ethyl phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 394 (S)-N-[[3-[3,5-Difluro-4-(4-formyl-1-piperazinyl)- P-139 Z (a) phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 395 (S)-N-[[3-[3,5-Difluro-4-(4-formyl-1-piperazinyl)- P-139 Z (b) phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl- propanethioamide 396 (S)-N-[[3-[3,5-Difluro-4-(4-formyl-1-piperazinyl)- P-139 Z (c) phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclo- propanecarbothioamide 397 (S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5- P-140 Ethyl oxazolidinyl]methyl]thioacetamide dithio- acetate 398 (S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5- P-140 Z (a) oxazolidinyl]methyl]propanethioamide 399 (S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5- P-140 Z (b) oxazolidinyl]methyl]-2-methylpropanethioamide 400 (S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5- P-140 Z (c) oxazolidinyl]methyl]cyclopropane-carbothioamide

When in the general procedure of Example 31, step 1, an appropriate amount of the amine listed below is substituted for compound 33, the isothiocyanate corresponding to the amines P-90, P-93, P-99, P-105, P-126 and P-129 are obtained.

When in the general procedure of Example 114 an appropriate amount of the isothiocyanate and the amine listed below are substituted for compound 82 and methylamine, the respective products listed below are obtained.

TABLE I Isothiocyanate Example Corresponding No. Product to Amine No. Amine 401 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 methylamine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 402 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 dimethylamine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′,N′-dimethylthiourea 403 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 azetidine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-1-azetidinecarbothioamide 404 (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)- P-90 anhydrous phenyl]-2-oxo-5-oxazolidinyl]methyl]- ammonia thiourea 405 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 methylamine piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 406 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 dimethylamine piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′,N′-dimethylthiourea 407 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 azetidine piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide 408 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 methylamine piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 409 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 dimethylamine piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′,N′-dimethylthiourea 410 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 azetidine piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-1-azetidinecarbothioamide 411 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)- P-105 methylamine 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 412 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)- P-105 dimethylamine 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′,N′-dimethylthiourea 413 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)- P-105 azetidine 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-1-azetidinecarbothioamide 414 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 methylamine piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 415 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 dimethylamine piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′,N′-dimethylthiourea 416 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 azetidine piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-1-azetidinecarbothioamide 417 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 methylamine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 418 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 dimethylamine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′,N′-dimethylthiourea 419 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 azetidine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-1-azetidinecarbothioamide

When in the general procedure of Example 100 an appropriate amount of the isothiocyanate and alcohol listed below are utilized in the same manner as Compound 82 and methanol are utilized, the respective products listed below are obtained.

TABLE J Isothiocyanate Example Corresponding No. Product to Amine No. Amine 420 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 methanol piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 421 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 ethanol piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-ethylthiocarbamate 422 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 isopropyl piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- alcohol methyl]-O-iso-propylthiocarbamate 423 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1- P-91 methanol piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 424 (S)-N-[[3-[4-(4-Acetyl-1- P-92 methanol piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 425 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 426 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 ethanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-ethylthiocarbamate 427 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93 isopropyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- alcohol methyl]-O-iso-propylthiocarbamate 428 (S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxy- P-94 methylaminel acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 429 (S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 methylamine piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 430 (S)-N-[3-[3-Fluoro-4-[4-(cyanoacetyl)-1- P-96 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 431 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)- P-97 methanol 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 432 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1- P-98 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 433 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 434 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 ethanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-ethylthiocarbamate 435 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99 isopropyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- alcohol methyl]-O-iso-propylthiocarbamate 436 (S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)- P-100 methanol 1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 437 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1- P-101 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 438 (S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)- P-102 methanol 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 439 (S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxy- P-103 methanol acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 440 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)- P-105 methanol 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 441 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)- P-105 ethanol 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-ethylthiocarbamate 442 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)- P-105 isopropyl 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- alcohol methyl]-O-iso-propylthiocarbamate 443 (S)-N-[[3-[3,5-Difluoro-4-[4-(methoxy- P-106 methanol carbonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 444 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 445 (S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)- P-108 methanol 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 446 (S)-N-[[3-[3,5-Difluoro-4-[4-(methane- P-109 methanol sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 447 (S)-N-[[3-[4-[4-(methanesulfonyl)-1- P-110 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 448 (S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1- P-111 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 449 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethane- P-112 methanol sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopropane- carbothioamide 450 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P-113 methanol piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 451 (S)-N-[[3-[3-Fluoro-4-[4-(chloromethane- P-114 methanol sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 452 (S)-N-[[3-[3,5-Difluoro-4-[4-(chloro- P-115 methanol methanesulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-O-methyl- thiocarbamate 453 (S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1- P-116 methanol piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 454 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane- P-117 methanol sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 455 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane- P-118 methanol sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 456 (S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1- P-119 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 457 (S)-N-[[3-[3-Fluoro-4-[4-(N-methyl- P-120 methanol sulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 458 (S)-N-[[3-[3,5-Difluoro-4-[4-(N-methyl- P-121 methanol sulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 459 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1- P-122 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 460 (S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethyl- P-123 methanol sulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 461 (S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethyl- P-124 methanol sulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 462 (S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1- P-125 methanol piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 463 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 464 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 ethanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-ethylthiocarbamate 465 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 isopropyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- alcohol methyl]-O-iso-propylthiocarbamate 466 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxy- P-127 methanol carbonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazidinyl]methyl]-O-methylthiocarbamate 467 (S)-N-[[3-[4-[4-(ethoxycarbonyl)-1- P-128 methanol piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 468 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 methanol piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate, 469 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 ethanol piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-ethylthiocarbamate 470 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 isopropyl piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- alcohol methyl]-O-iso-propylthiocarbamate 471 (S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1- P-130 methanol piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 472 (S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)- P-131 methanol phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- methylthiocarbamate 473 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1- P-132 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 474 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)- P-133 methanol 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 475 (S)-N-[[3-[4-[4-(cyanomethyl)-1- P-134 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 476 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1- P-135 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 477 (S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)- P-136 methanol 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 478 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P-137 methanol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-mehtylthiocarbamate 479 (S)-N-[[3-[3-Fluoro-4-(4-formyl-1- P-138 methanol piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 480 (S)-N-[[3-[3,5-Difluro-4-(4-formyl-1- P-139 methanol piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 481 (S)-N-[[3-[4-(4-formyl-1-piperazinyl)- P-140 methanol phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- methylthiocarbamate

EXAMPLE 482 (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidiny]methyl]thioacetamide, thiazepine S-oxide

Step 1. Hexahydro-5-oxo-1,4-thiazepine is prepared according to the procedure described by Gallego (J. Org. Chem. 1993, 58, 3905-3911).

Step 2. Lithium aluminum hydride (5.5 mL of a 1M solution in THF) is added dropwise to a stirred solution of hexahydro-5-oxo-1,4-thiazepine (721.5 mg) in dry THF (21 mL) cooled to 0° C. The reaction mixture is stirred at 0° C. for 10 min, then at room temperature for 4 h. The reaction mixture is quenched by careful successive addition of water (0.2 mL), 5N aqueous NaOH (0.2 mL) and water (0.74 mL). The reaction mixture becomes very thick and gel-like. The reaction mixture is diluted with ether (50 mL) and filtered through a pad of celite. The filter cake is washed with ether (100 mL). The filtrate is concentrated to afford 616.6 mg of 1,4-hexahydrothiazepine which is used immediately in the next step.

Step 3. To a stirred solution of 1,4-hexahydrothiazepine (596.0 mg) and 3,4-difluoronitrobenzene (0.51 mL) in acetonitrile (14 mL) is added diisopropylethylamine (1.0 mL). The yellow solution is heated at reflux for 18 h, then cooled and concentrated. The residue is diluted with CH₂Cl₂ (100 mL) and washed with saturated aqueous NH₄Cl (35 mL). The phases are separated and the organics are dried (MgSO₄), filtered and concentrated. The residue is purified by flash chromatography using 20% EtOAc in hexane as the eluent to afford 830.2 mg of the nitrobenzene. Mp 115-116° C.; Anal. Calcd for C₁₁H₁₃FN₂O₂S: C, 51.55; H, 5.1 1; N, 10.93; S, 12.51. Found: C, 51.47, H, 5.12; N, 10.79; S, 12.42.

Step 4. To a stirred suspension of the nitrobenzene prepared in Step 3 (5.5 g) in EtOH (260 mL) is added a solution of 2M aqueous CuSO₄ (11.9 mL). The mixture is s cooled to 0° C. and NaBH₄ (4.1 g) is added in portions. The reaction mixture turns very dark and is stirred at 0° C. for 10 min, at room temperature for 30 min, and then heated at reflux for 3 h. The cooled reaction mixture is diluted with EtOAc (500 ml) and washed with water (200 mL). The aqueous mixture is extracted with EtOAc (3×200 mL). The combined organics are dried (MgSO₄), filtered and concentrated to afford the aniline intermediate.

Step 5. The dark residue from Step 4 is dissolved in 2:1 acetone/water (255 mL) and cooled to 0° C. To this stirred mixture is added solid NaHCO₃ (5.4 g) followed by benzylchloroformate (7.7 mL). The reaction mixture is stirred at 0° C. for 10 min, then at room temperature for 24 h. The reaction mixture is quenched with 10% aqueous NaHSO₄ (200 mL) and then poured into EtOAc (300 mL). The phases are separated and the aqueous phase is extracted with EtOAc (2×250 mL). The combined organics are dried (MgSO₄), filtered and concentrated. The residue is purified by MPLC using 20% EtOAc in hexane to afford 6.03 g of the benzylcarbamate as a yellow solid. mp 72-74° C.; Anal. Calcd for C₁₉H₂₁FN₂O₂S: C, 63.31; H, 5.87; N, 7.77; S, 8.89. Found: C, 63.31; H, 5.97; N, 7.69; S, 8.79.

Step 6. To a stirred solution of the carbamate from Step 5 (3.0 g) in dry THF (33 mL) under N₂ cooled to −78° C., is added dropwise via syringe a 1.6M solution of nBuLi in hexane (5.4 mL). The reaction mixture was stirred at −78° C. for 35 min, then R-glycidyl butyrate (1.2 mL) is added. The reaction mixture is stirred at −78° C. for 30 min, then at room temperature overnight during which time a precipitate forms. The reaction mixture is quenched with saturated aqueous NH₄Cl (33 mL) and poured into EtOAc (100 mL). The phases are separated. The organic phase is washed with saturated aqueous NaHCO₃ (50 mL), brine (50 mL), dried (MgSO₄), filtered and concentrated. The residue is purified by flash chromatography using EtOAc as the eluent to afford 2.5 g of a hydroxymethyl oxazolidinone. Mp 100-102° C. Anal. Calcd for C₁₅H₁₉FN₂O₃S: C,55.20; H, 5.87; N, 8.58; S, 9.82. Found: C, 55.09; H, 5.91; N, 8.36; S, 9.57.

Step 7. To a stirred solution of the alcohol prepared in Step 6 (1.7 g) in CH₂Cl₂ (35 mL) cooled to 0° C., is added triethylamine (1.1 mL) followed by methanesulfonyl chloride (0.5 mL). The reaction mixture is stirred at 0° C. for 10 min, then at room temperature for 1 h. The reaction mixture is treated with water (35 mL). The phases are separated and the aqueous phase is extracted with CH₂Cl₂ (35 mL). The combined organic phases are dried (MgSO₄), filtered and concentrated. The residue is purified by flash chromatography using 80% EtOAc in hexane as the eluent to afford 2.1 g of the mesylate. Mp 132-142° C. Anal. Calcd for C₁₆H₂₁FN₂O₅S₂: C, 47.51; H, 5.23; N, 6.93; S, 15.85. Found: C, 47.18; H, 5.28; N, 6.84; S, 15.60.

Step 8. Ammonia gas is bubbled into a stirred suspension of the mesylate prepared in Step 7 (941.7 mg) in 1:1 THF/CH₃OH (40 mL) until saturated (approx. 5 min). The reaction mixture is heated in a sealed tube at 100° C. for 72 h. The cooled reaction mixture is concentrated to give the crude amine, which is immediately suspended in CH₂Cl₂ (35 mL) and cooled to 0° C. To this stirred suspension is added triethylamine (0.97 mL, 6.9 mmol) followed by di-tert-butyl dicarbonate (759.5 mg, 3.5 mmol). The reaction mixture becomes homogeneous and is stirred at RT for 18 h. The reaction mixture is poured into CH₂Cl₂ (75 mL) and washed with H₂O (1×50 mL). The organic phase is dried (MgSO₄), filtered and concentrated. The resulting residue is purified on a Biotage 40 S column using 30-35% ethyl acetate in CH₃OH as the eluent to afford 867.4 mg of the protected amine. mp 74-75° C. Anal Cald: C, 56.45; H, 6.63; N, 9.88. Found: C, 56.95; H, 6.85; N, 9.55.

Step 9. To a stirred suspension of the protected amine prepared in Step 8 (205.2 mg) in 1:1 CH₃OH/H₂O (6 mL) cooled to 0° C. is added sodium meta periodate (113.5 mg). The resulting suspension is stirred at RT for 18 h. The reaction mixture is filtered and the solid is washed with CH₂Cl₂ (2×20 mL). The filtrate is extracted with H₂O (1×10 mL). The phases are separated. The aqueous phase is extracted with CH₂Cl₂ (1×25 mL). The combined organic phases are dried (MgSO₄), filtered and concentrated. The white solid residue is purified on a Biotage 12M column using 5% CH₃OH in CH₂Cl₂ as the eluent to afford 187.3 mg of the sulfoxide. mp 78-81° C.

Step 10. Dry HCl gas is passed over the surface of a stirred solution of the sulfoxide prepared in Step 9 (179.3 mg) in CH₃OH (2 mL) cooled to 0° C. for 1 minute. The reaction mixture is stirred at 0° C. for 10 min, then at room temperature for 15 min, then concentrated. The resulting yellow residue is suspended in THF (5 mL) and CH₂Cl₂ (5 mL) and cooled to 0° C. To this stirred suspension is added triethylamine (0.46 mL) followed by ethyldithioacetate (0.18 mL). The dark reaction mixture is stirred at RT overnight then concentrated. The dark residue is diluted with CH₂Cl₂ (30 mL) and washed with H₂O (2×15 mL). The organic phases are dried (MgSO₄), filtered and concentrated. The dark residue is purified on a Biotage 12M column using 5% CH₃OH in CH₂Cl₂ as the eluent to afford 71.5 mg of the title compound as a tan solid. mp 85-89° C.

Following the general procedure outlined in Step 10 of Example 482, but substituting the dithioesters listed below, the compounds of Examples 483 to 495 of Table K can be obtained.

TABLE K Example Dithioester No. Compound Amine (from Preparation Z) 483 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepine S-oxide

Z (a) 484 S)-N-[[3-[3-Fluoro-4- Same as above Z (b) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S- oxide. 485 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (c) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S- oxide. 486 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (d) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide, thiazepine S-oxide 487 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (e) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide, thiazepine S-oxide 488 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (f) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide, thiazepine S-oxide 489 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (g) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide, thiazepine S- oxide 490 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (h) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothio- amide, thiazepine S- oxide 491 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (i) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- cyclopentanecarbothio- amide, thiazepine S- oxide 492 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (j) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothio- amide, thiazepine S- oxide 493 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (k) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide, thiazepine S- oxide 494 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (l) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide, thiazepine S- oxide 495 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (m) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethio- amide, thiazepine S- oxide

EXAMPLE 496 (5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)-phenyl-]2oxo-5-oxazolinminyl]methyl]thioacetamide, thiazepine S-oxide

The title compound can be prepared by the procedure of Example 482, by substituting an appropriate quantity of 2,6-difluoro-4-nitrobenzene (trifluoromethane) sulfonate for 3,4-difluoronitrobenzene in Step 1.

Utilizing the amine prepared in Example 496, but substituting the dithioester listed below for ethyl dithioacetate in the final step, the compounds of Examples 497 to 499 of Table L are obtained.

TABLE L Example Dithioester No. Compound Amine (from Preparation Z) 497 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepine S-oxide

Z (a) 498 (5S)-N-[[3-[3,5- Same as above Z (b) Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S- oxide 499 (5S)-N-[[3-[3,5- Same as above Z (c) Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S- oxide

EXAMPLE 500 (5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S-oxide.

The title compound can be prepared by the procedure of Example 482, by substituting an appropriate quantity of 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in Step 1.

Utilizing the amine prepared in Example 500, but substituting the dithioester listed below for ethyl dithioacetate in the final step, the compounds of Examples 501 to 503 of Table M are obtained

TABLE M Example Dithioester No. Compound Amine (from Preparation Z) 501 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepine S-oxide

Z (a) 502 (5S)-N-[[3-[4- Same as above Z (b) (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S- oxide 503 (5S)-N-[[3-[4- Same as above Z (c) (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S- oxide

EXAMPLE 504 (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S,S-dioxide

Step 1. To a stirred solution of the thiazepine prepared in Step 8 of Example 482 (243.7 mg) in 25% H₂O/acetone (8 mL) is added 4-methylmorpholine N-oxide (201.5 mg) followed by a solution of osmium tetroxide in 2-methyl-2-propanol (2.5 wt %, 30 μL). The reaction mixture is stirred at room temperature for 18 h. The reaction mixture is treated with saturated sodium bisulfate (8 mL), then poured into CH₂Cl₂ (50 mL). The phases are separated. The aqueous phase is extracted with CH₂Cl₂ (2×25 mL). The combined organic phases are washed with brine (1×25 mL), dried (MgSO₄), filtered and concentrated. The residue is purified on a Biotage 40 S column using 1% CH₃OH in CH₂Cl₂ as the eluent to afford 216.1 mg (0.47 mmol, 83%) of the thiazepine S,S-dioxide as a white solid. mp 144-146° C.

Step 2. Dry HCl gas is passed over the surface of a stirred solution of the thiazepine S,S-dioxide prepared in Step 1 (108.2 mg) in CH₃OH(3 mL) at 0° C. for 1 minute. The reaction mixture is stirred at 0° C. for 10 min and then at room temperature for 15 min. The reaction is concentrated and the yellow residue is suspended in CH₂Cl₂ (2 mL) and THF (2 mL). This stirred suspension is cooled to 0° C. and triethylamine (0.27 mL) is added followed by a solution of ethyldithioacetate (0.11 mL) in THF (0.5 mL) with 0.25 mL rinse. The yellowish-green solution is stirred at 0° C. for 10 min then at room temperature for 18 h. The reaction mixture is poured into CH₂Cl₂ (20 mL) and washed with H₂O (2×10 mL). The organic phase was dried (MgSO₄), filtered and concentrated. The residue is purified on a Biotage 12M column using 2% CH₃OH in CH₂Cl₂ as the eluent to afford 77.3 mg of the title compound as a white solid. mp 88-90° C.

Following the general procedure outlined in Step 2 of Example 504, but substituting the dithioester listed below for ethyl dithioacetate, the compounds of Examples 505 to 507 of Table N are obtained.

TABLE N Example Dithioester No. Compound Amine (from Preparation Z) 505 (5S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methy1]- propanethioamide, thiazepine S,S-dioxide

Z (a) 506 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (b) (4-thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S,S- dioxide 507 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (c) (4-thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S,S- dioxide

EXAMPLE 508 (5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S,S-dioxide

The title compound can be prepared by the procedures of Examples 504 and 482, by substituting an appropriate quantity of 2,6-difluoro-4-nitrobenzene (trifluoromethane) sulfonate for 3,4-difluoronitrobenzene in Step 1 of Example 482.

Utilizing the amine prepared in Example 508, but substituting the dithioester listed below for ethyl dithioacetate in the final step, the compounds of Examples 509 to 511 of Table O are obtained.

TABLE O Example Dithioester No. Compound Amine (from Preparation Z) 509 (5S)-N-[[3-[3,5- Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepine S,S-dioxide

Z (a) 510 (5S)-N-[[3-[3,5- Same as above Z (b) Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S,S- dioxide 511 (5S)-N-[[3-[3,5- Same as above Z (c) Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S,S- dioxide

EXAMPLE 512 (5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiazepine S,S-dioxide

The title compound can be prepared by the procedure of Examples 504 and 482, by substituting an appropriate quantity of 4-fluoronitrobenzene for 3,4-difluoronitro-benzene in Step 1 of Example 482.

Utilizing the amine prepared in Example 512, but substituting the dithioester listed below for ethyl dithioacetate in the final step, the compounds of Examples 513 to 515 of Table P are obtained.

TABLE P Example Dithioester No. Compound Amine (From Preparation Z) 513 (5S)-N-[[3-[4- (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo-5- oxazolidinyl]- methyl]propanethio- amide, thiazepine S,S- dioxide

Z (a) 514 (5S)-N-[[3-[4- Same as above Z (b) (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S,S- dioxide 515 (5S)-N-[[3-[4- Same as above Z (c) (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo-5- oxazolidinyl]- methyl]cyclopropane- carbothioamide, thiazepine S,S-dioxide

EXAMPLE 516 (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide.

This compound is prepared according to the procedure of Step 8 in Example 482, but substituting an appropriate quantity of ethyl dithioacetate for di-tert-butyl dicarbonate; mp 129-131° C.

Utilizing the amine prepared in Step 8 of Example 482, but substituting an appropriate quantity of the dithioester listed below for di-tert-butyl dicarbonate, the compounds of Examples 517 to 529 of Table Q are obtained.

TABLE Q Example Dithioester No. Compound Amine (From Preparation Z) 517 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide

Z (a) 518 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (b) (tetrahydro-1,4- thiazepin-4(5H)yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 519 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (c) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide 520 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (d) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide 521 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (e) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide 522 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (f) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide 523 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (g) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide 524 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (h) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothioamide 525 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (i) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothio- amide 526 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (j) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothio- amide 527 (5S)-N-[[3-[3-5 Fluoro- Same as above Z (k) 4-(tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide 528 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (l) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide 529 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (m) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethioamide

EXAMPLE 530 (5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

This compound can be prepared according to the procedures of Example 482 and Example 516, but substituting an appropriate quantity of 2,6-difluoro-4-nitrophenyl trifluoromethane sulfonate for 3,4-difluoronitrobenzene in Step 1 of Example 482.

Utilizing the amine prepared in Example 530, but substituting an appropriate quantity of the dithioester listed below for di-tert-butyl dicarbonate, the compounds of Examples 531 to 533 of Table R can be prepared.

TABLE R Example Dithio Compound No. Compound Amine (from Preparation Z) 531 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide

Z (a) 532 (5S)-N-[[3-[3,5- Same as above Z (b) Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 523 (5S)-N-[[3-[3,5- Same as above Z (c) Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide

EXAMPLE 534 (5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide; mp 129-131° C.

This compound can be prepared according to the procedures of Example 482 and Example 516, but substituting an appropriate quantity of 4-fluoronitrobenzene for 3,4-difluoronitrobenzene in Step 1 of Example 482.

Utilizing the amine prepared in Example 534, but substituting an appropriate quantity of the dithioester listed below for di-tert-butyl dicarbonate, the compounds of Examples 535 to 537 of Table S can be prepared.

TABLE S Example Dithio Compound No. Compound Amine (from Preparation Z) 535 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]- methyl]propanethio- amide

Z (a) 536 (5S)-N-[[3-[4- Same as above Z (b) (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 537 (5S)-N-[[3-[4- Same as above Z (c) (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]- methyl]cyclopropane- carbothioamide

EXAMPLE 538 (5S)-N-[[3-[3-Fluoro4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S-oxide

This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 482 for the amine 33.

By reaction of the isothiocyanate prepared in Example 538 with the amines and alcohols listed in Table T, the compounds of Examples 539 to 544 can be prepared.

TABLE T Example Amine or No. Compound Isothiocyanate Alcohol 539 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S-oxide

CH₃NH₂ 540 (5S)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂NH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S-oxide 541 (5S)-N-[[3-[3-Fluoro-4- Same as above Azetidine (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S-oxide 542 (5S)-N-[[3-[3-Fluoro-4- Same as above CH₃OH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S-oxide 543 (5S)-N-[[3-[3-Fluoro-4- Same as above CH₃CH₂OH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S-oxide 544 (5S)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂CHOH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S-oxide

EXAMPLE 545 (5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S-oxide

This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 496 for the amine 33.

By reaction of the isothiocyanate prepared in Example 545 with the amines and alcohols listed in Table U, the compounds of Examples 546 to 551 can be prepared.

TABLE U Example Amine or No. Compound Isothiocyanate Alcohol 546 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S-oxide

CH₃NH₂ 547 (5S)-N-[[3-[3,5- Same as above (CH₃)₂NH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S-oxide 548 (5S)-N-[[3-[3,5- Same as above Azetidine Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S-oxide 549 (5S)-N-[[3-[3,5- Same as above CH₃OH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S-oxide 550 (5S)-N-[[3-[3,5- Same as above CH₃CH₂OH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S-oxide 551 (5S)-N-[[3-[3,5- Same as above (CH₃)₂CHOH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S-oxide

EXAMPLE 552 (5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S-oxide

This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 500 for the amine 33.

By reaction of the isothiocyanate prepared in Example 552 with the amines and alcohols listed in Table V, the compounds of Examples 553 to 558 can be prepared.

TABLE V Example Amine or No. Compound Isothiocyanate Alcohol 553 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S-oxide

CH₃NH₂ 554 (5S)-N-[[3-[4- Same as above (CH₃)₂NH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S-oxide 555 (5S)-N-[[3-[4- Same as above Azetidine (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S-oxide 556 (5S)-N-[[3-[4- Same as above CH₃OH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S-oxide 557 (5S)-N-[[3-[4- Same as above CH₃CH₂OH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S-oxide 558 (5S)-N-[[3-[4- Same as above (CH₃)₂CHOH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S-oxide

EXAMPLE 559 (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S,S-dioxide

This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 504 for the amine 33.

By reaction of the isothiocyanate prepared in Example 559 with the amines and alcohols listed in Table W, the compounds of Examples 560 to 565 can be prepared.

TABLE W Example Amine or No. Compound Isothiocyanate Alcohol 560 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S,S-dioxide

CH₃NH₂ 561 (5S)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂NH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S,S-dioxide 562 (5S)-N-[[3-[3-Fluoro-4- Same as above Azetidine (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S,S-dioxide 563 (5S)-N-[[3-[3-Fluoro-4- Same as above CH₃OH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S,S-dioxide 564 (5S)-N-[[3-[3-Fluoro-4- Same as above CH₃CH₂OH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S,S-dioxide 565 (5S)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂CHOH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S,S-dioxide

EXAMPLE,566 (5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiazepine S,S-dioxide

This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 508 for the amine 33.

By reaction of the isothiocyanate prepared in Example 566 with the amines and alcohols listed in Table X, the compounds of Examples 561 to 572 can be prepared.

TABLE X Example Amine or No. Compound Isothiocyanate Alcohol 567 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S,S-dioxide

CH₃NH₂ 568 (5S)-N-[[3-[3,5- Same as above (CH₃)₂NH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S,S-dioxide 569 (5S)-N-[[3-[3,5- Same as above Azetidine Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S,S-dioxide 570 (5S)-N-[[3-[3,5- Same as above CH₃OH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S,S-dioxide 571 (5S)-N-[[3-[3,5- Same as above CH₃CH₂OH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S,S-dioxide 572 (5S)-N-[[3-[3,5- Same as above (CH₃)₂CHOH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S,S-dioxide

EXAMPLE 573 (5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo5-oxazolidinyl]methyl]thiourea, thiazepine S,S-dioxide

This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 512 for the amine 33.

By reaction of the isothiocyanate prepared in Example 573 with the amines and alcohols listed in Table Y, the compounds of Examples 574 to 579 can be prepared.

TABLE Y Example Amine or No. Compound Isothiocyanate Alcohol 574 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S,S-dioxide

CH₃NH₂ 575 (5S)-N-[[3-[4- Same as above (CH₃)₂NH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S,S-dioxide 576 (5S)-N-[[3-[4- Same as above Azetidine (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S,S-dioxide 577 (5S)-N-[[3-[4- Same as above CH₃OH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate, thiazepine S,S-dioxide 578 (5S)-N-[[3-[4- Same as above CH₃CH₂OH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S,S-dioxide 579 (5S)-N-[[3-[4- Same as above (CH₃)₂CHOH (Tetrahydro-1,4- thiazepin-4(5H)- y1)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S,S-dioxide

EXAMPLE 580 (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Step 8 of Example 482 for the amine 33.

By reaction of the isothiocyanate prepared in Example 580 with the amines and alcohols listed in Table Z, the compounds of Examples 581 to 586 can be prepared.

TABLE Z Example Amine or No. Compound Isothiocyanate Alcohol 581 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea

CH₃NH₂ 582 (5H)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂NH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea 583 (5S)-N-[[3-[3-Fluoro-4- Same as above Azetidine (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide 584 (5S)-N-[[3-[3-Fluoro-4- Same as above CH₃OH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate 585 (5S)-N-[[3-[3-Fluoro-4- Same as above CH₃CH₂OH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate 586 (5S)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂CHOH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate

EXAMPLE 587 (5S)-N-[[3-3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 530 for the amine 33.

By reaction of the isothiocyanate prepared in Example 587 with the amines and alcohols listed in Table AA, the compounds of Examples 588 to 593 can be prepared.

TABLE AA Example Amine or No. Compound Isothiocyanate Alcohol 588 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea

CH₃NH₂ 589 (5S)-N-[[3-[3,5- Same as above (CH₃)₂NH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea 590 (5S)-N-[[3-[3,5- Same as above Azetidine Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide 591 (5S)-N-[[3-[3,5- Same as above CH₃OH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate 592 (5S)-N-[[3-[3,5- Same as above CH₃CH₂OH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate 593 (5S)-N-[[3-[3,5- Same as above (CH₃)₂CHOH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate

EXAMPLE 594 (5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

This compound can be prepared by the procedure described in Example 33, but substituting the amine prepared in Example 534 for the amine 33.

By reaction of the isothiocyanate prepared in Example 594 with the amines and alcohols listed in Table BB, the compounds of Examples 595 to 600 can be prepared.

TABLE BB Example Amine or No Compound Isothiocyanate Alcohol 595 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea

CH₃NH₂ 596 (5S)-N-[[3-[4- Same as above (CH₃)₂NH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea 597 (5S)-N-[[3-[4- Same as above Azetidine (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide 598 (5S)-N-[[3-[4- Same as above CH₃OH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate 599 (5S)-N-[[3-[4- Same as above CH₃CH₂OH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate 600 (5S)-N-[[3-[4- Same as above (CH₃)₂CHOH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate 

What is claimed:
 1. A compound of the formula I

or a pharmaceutical acceptable salt thereof wherein: G is

R₁ is (1) H, (2) NH₂, (3) NHC₁₋₄alkyl, (4) C₁₋₄alkyl, (5) —OC₁₋₄alkyl, (6) —SC₁₋₄alkyl, (7) C₁₋₄alkyl substituted with one to three fluoro, one to two chloro, CN or —COOC₁₋₄alkyl, (8) C₃₋₆cycloalkyl, (9) N(C₁₋₄alkyl)₂, or (10) N(CH₂)₂₋₅; A is

R₂₃ and R₂₄ are independently (1) H, (2) F, (3) Cl, (4) C₁₋₂alkyl, (5) CN, (6) OH, (7) C₁₋₂alkoxy, (8) nitro, or (9) amino; Q is

Z² is (1) —O₂S—, (2) —O—, (3) —OS—, or (4) —S—; and w is 0 or
 1. 2. A compound of formula I as shown in claim 1 which is


3. A compound of claim 2 wherein R₂₃ and R₂₄ are independently H or F.
 4. A compound of claim 3 wherein Z² is —SO₂—, —SO—, or —S—.
 5. A compound of claim 3 wherein Z² is —O—.
 6. A compound of claim 3 wherein w is
 1. 7. A compound of claim 3 wherein w is
 1. 8. A compound of claim 6 wherein R₁ is (1) H, (2) NH₂, (3) NHC₁₋₄alkyl, (4) C₁₋₄alkyl, (5) —OC₁₋₄alkyl, (6) —SC₁₋₄alkyl, (7) C₁₋₄alkyl substituted with one to two Cl, (8) C₃₋₆cycloalkyl, or (9) N(C₁₋₄alkyl)₂.
 9. A compound of claim 7 wherein R₁ is (1) H, (2) NH₂, (3) NHC₁₋₄alkyl, (4) C₁₋₄alkyl, (5) —OC₁₋₄alkyl, (6) —SC 1-4alkyl, (7) C₁₋₄alkyl substituted with one to two Cl, (8) C₃₋₆cycloalkyl, or (9) N(C₁₋₄alkyl)₂.
 10. A compound of claim 2 which is (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiomorpholine S-oxide.
 11. A compound of claim 2 which is (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-propanethioamide, thiomorpholine S-oxide; (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, thiomorpholine S-oxide; (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothio-amide, thiomorpholine S-oxide; (S)-N-[[3-[3-fluoro-4-(4thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-methylthiocarbamate, thiomorpholine S-oxide; (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate, thiomorpholine S-oxide; (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiomorpholine S-oxide; (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea, thiomorpholine S-oxide; or (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyll-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiomorpholine S-oxide.
 12. A compound of claim 2 which is (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-ethylthiocarbamate; (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide; (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropane-carbothioamide.
 13. A method for treating microbial infections in humans and other warm blooded animals comprising administering to humans and other warm blooded animals in need for such treatment thereof an effective amount of a compound of formula I as shown in claim
 1. 14. The method of claim 13 wherein said compound of formula I is administered orally, parenterally, or topically.
 15. The method of claim 13 wherein said compound is administered in an amount of from about 0.1 to about 100 mg/kg of body weight/day.
 16. The method of claim 13 wherein said compound is administered in an amount of from about 1 to about 50 mg/kg of body weight/day.
 17. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
 18. A compound of claim 2 which is 1) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, (2) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl] methyl]thiourea, (3) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N'-methylthiourea, (4) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-thioformamide, (5) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl] methyl]thiopropion-amide, (6) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-chlorothioacetamide, (7) (S)-N-[[3-[3-fluoro-4-(4-moropholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]α,α,α-trifluorothioacetamide, (8) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-fluorothioacetamide, (9) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- α,α-difluorothioacetamide, (10) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-cyanothioacetamide, (11) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- α,α -dichlorothioacetamide, (12) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-(methoxycarbonyl)thioacetamide, (13) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide, (14) (S)-N-[[3-[3-fFluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] thio-acetamide, thiomorpholine S-oxide, (15) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide, thiomorpholine S, S-dioxide, (16) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea, thiomorpholine S-oxide, (17) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl-S-methyldithiocarbamate, (18) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl-O-methylthiocarbamate, (19) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-ethylthiocarbamate, (20) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, (21) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane-carbothioamide, (22) (S)-N-[[3-[3,5-difluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-thioacetamide, (23) (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea, (24) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-propanethioamide, thiomorpholine S-oxide, (25) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, thiomorpholine S-oxide, (26) (S)-N-[[3-[3-fFlouro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothio-amide, thiomorpholine S-oxide, (27) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-butanethioamide, thiomorpholine S-oxide, (28) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-methylbutanethioamide, thiomorpholine S-oxide, (29) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutanethioamide, thiomorpholine S-oxide, (30) (S)-N-[[3-[3-fFluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide, thiomorpholine S-oxide, (31) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclobutanecarbothioamide, thiomorpholine S-oxide, (32) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-cyclopentanecarbothioamide, thiomorpholine S-oxide, (33) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclohexanecarbothioamide, thiomorpholine S-oxide, (34) (S)-N-[[3-[3-fFluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopropylethanethioamide, thiomorpholine S-oxide, (35) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethanethioamide, thiomorpholine S-oxide, (36) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide, thiomorpholine S-oxide, (37) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiomorpholine S-oxide, (38) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide, thiomorpholine S-oxide, (39) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, thiomorpholine S-oxide, (40) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide, thiomorpholine S-oxide, (41) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiomorpholine S-oxide, (42) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide, thiomorpholine S-oxide, (43) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, thiomorpholine S-oxide, (44) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide, thiomorpholine S-oxide, (45) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide, thiomorpholine S,S-dioxide, (46) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, thiomorpholine S,S-dioxide, (47) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide, thiomorpholine S,S-dioxide, (48) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, thiomorpholine S,S-dioxide, (49) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide, thiomorpholine S,S-dioxide, (50) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, thiomorpholine S,S-dioxide, (51) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide, thiomorpholine S,S-dioxide, (52) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiomorpholine S,S-dioxide, (53) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide, thiomorpholine S,S-dioxide, (54) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl propanethioamide, thiomorpholine S,S-dioxide, (55) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide, thiomorpholine S,S-dioxide, (56) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide, (57) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, (58) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide, (59) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]butanethioamide, (60) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-methylbutanethioamide, (61) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutanethioamide, (62) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide, (63) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclobutanecarbothioamide, (64) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopentanecarbothioamide, (65) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclohexanecarbothioamide, (66) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopropylethanethioamide, (67) (S)-N-[[3-[3-dluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethanethioamide, (68) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide, (69) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, (70) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide, (71) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide, (72) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide, (73) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, (74) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide, (75) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl propanethioamide, (76) (S)-N-[[3-[4-(4-thimorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide, (77) (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S-oxide, (78) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S-oxide, (79) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S-oxide, (80) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S,S-dioxide, (81) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S,S-dioxide, (82) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S,S-dioxide, (83) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, (84) (S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, (85) (S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, (86) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate, thiomorpholine S-oxide, (87) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiomorpholine S-oxid, (88) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate, (89) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-iso-propylthiocarbamate, (90) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea, thiomorpholine S-oxide, (91) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea, thiomorpholine S-oxide, (92) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiomorpholine S-oxide, (93) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methyl-N′-methylthiourea, (94) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea, (95) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide, or (96) (S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide. 